SpringerLink
Log in

Understanding the CREB1-miRNA feedback loop in human malignancies

  • Review
  • Published:
Tumor Biology

Abstract

cAMP response element binding protein 1 (CREB1, CREB) is a key transcription factor that mediates transcriptional responses to a variety of growth factors and stress signals. CREB1 has been shown to play a critical role in development and progression of tumors. MicroRNAs (miRNAs) are a class of non-coding RNAs. They post-transcriptionally regulate gene expression through pairing with the 3′-UTR of their target mRNAs and thus regulate initiation and progression of various types of human cancers. Recent studies have demonstrated that a number of miRNAs can be transcriptionally regulated by CREB1. Interestingly, CREB1 expression can also be modulated by miRNAs, thus forming a feedback loop. This review outlines the functional roles of CREB1, miRNA, and their interactions in human malignancies. This will help to define a relationship between CREB1 and miRNA in human cancer and develop novel therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Weinstein IB. Growth factors, oncogenes, and multistage carcinogenesis. J Cell Biochem. 1987;33(3):213–24. doi:10.1002/jcb.240330308.

    Article  CAS  PubMed  Google Scholar 

  2. Ito Y. Signals and transcription factors. Gan To Kagaku Ryoho Cancer Chemother. 1989;16(3 Pt 2):509–15.

    CAS  Google Scholar 

  3. Hsieh WT, Tzeng KR, Ciou JS, Tsai JJ, Kurubanjerdjit N, Huang CH, et al. Transcription factor and microRNA-regulated network motifs for cancer and signal transduction networks. BMC Syst Biol. 2015;9 Suppl 1:S5. doi:10.1186/1752-0509-9-s1-s5.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Shaywitz AJ, Greenberg ME. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. 1999;68:821–61. doi:10.1146/annurev.biochem.68.1.821.

    Article  CAS  PubMed  Google Scholar 

  5. Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, et al. TORCs: transducers of regulated CREB activity. Mol Cell. 2003;12(2):413–23.

    Article  CAS  PubMed  Google Scholar 

  6. Siu YT, ** DY. CREB—a real culprit in oncogenesis. FEBS J. 2007;274(13):3224–32. doi:10.1111/j.1742-4658.2007.05884.x.

    Article  CAS  PubMed  Google Scholar 

  7. Shankar DB, Cheng JC, Kinjo K, Federman N, Moore TB, Gill A, et al. The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia. Cancer Cell. 2005;7(4):351–62. doi:10.1016/j.ccr.2005.02.018.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, et al. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A. 2005;102(12):4459–64. doi:10.1073/pnas.0501076102.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Impey S, McCorkle SR, Cha-Molstad H, Dwyer JM, Yochum GS, Boss JM, et al. Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell. 2004;119(7):1041–54. doi:10.1016/j.cell.2004.10.032.

    CAS  PubMed  Google Scholar 

  10. Maureira A, Sanchez R, Valenzuela N, Torrejon M, Hinrichs MV, Olate J, et al. The CREB transcription factor controls transcriptional activity of the human RIC8B gene. J Cell Biochem. 2016. doi:10.1002/jcb.25479.

    PubMed  Google Scholar 

  11. Mylroie H, Dumont O, Bauer A, Thornton CC, Mackey J, Calay D, et al. PKCepsilon-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis. Cardiovasc Res. 2015;106(3):509–19. doi:10.1093/cvr/cvv131.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11(9):597–610. doi:10.1038/nrg2843.

    CAS  PubMed  Google Scholar 

  13. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524–9. doi:10.1073/pnas.242606799.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999–3004. doi:10.1073/pnas.0307323101.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM. MicroRNA expression and function in cancer. Trends Mol Med. 2006;12(12):580–7. doi:10.1016/j.molmed.2006.10.006.

    Article  CAS  PubMed  Google Scholar 

  16. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8. doi:10.1038/nature03702.

    Article  CAS  PubMed  Google Scholar 

  17. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61. doi:10.1073/pnas.0510565103.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. doi:10.1038/nrc1997.

    Article  CAS  PubMed  Google Scholar 

  19. Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014;9:287–314. doi:10.1146/annurev-pathol-012513-104715.

    Article  PubMed  CAS  Google Scholar 

  20. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  CAS  PubMed  Google Scholar 

  21. Bertoli G, Cava C, Castiglioni I. MicroRNAs: new biomarkers for diagnosis, prognosis, therapy prediction and therapeutic tools for breast cancer. Theranostics. 2015;5(10):1122–43. doi:10.7150/thno.11543.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Chivukula RR, Mendell JT. Circular reasoning: microRNAs and cell-cycle control. Trends Biochem Sci. 2008;33(10):474–81. doi:10.1016/j.tibs.2008.06.008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 2009;37(Pt 4):918–25. doi:10.1042/bst0370918.

    Article  CAS  PubMed  Google Scholar 

  24. Ozsolak F, Poling LL, Wang Z, Liu H, Liu XS, Roeder RG, et al. Chromatin structure analyses identify miRNA promoters. Genes Dev. 2008;22(22):3172–83. doi:10.1101/gad.1706508.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Corcoran DL, Pandit KV, Gordon B, Bhattacharjee A, Kaminski N, Benos PV. Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS ONE. 2009;4(4):e5279. doi:10.1371/journal.pone.0005279.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447(7148):1130–4. doi:10.1038/nature05939.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435(7043):839–43. doi:10.1038/nature03677.

    Article  PubMed  CAS  Google Scholar 

  28. Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2008;40(1):43–50. doi:10.1038/ng.2007.30.

    Article  CAS  PubMed  Google Scholar 

  29. Tan X, Wang S, Yang B, Zhu L, Yin B, Chao T, et al. The CREB-miR-9 negative feedback minicircuitry coordinates the migration and proliferation of glioma cells. PLoS ONE. 2012;7(11):e49570. doi:10.1371/journal.pone.0049570.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Zhang Y, Yang J, Cui X, Chen Y, Zhu VF, Hagan JP, et al. A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth. EMBO Mol Med. 2013;5(9):1322–34. doi:10.1002/emmm.201302507.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Zhang JQ, Yao QH, Kuang YQ, Ma Y, Yang LB, Huang HD, et al. Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human Astrocytoma. Hum Pathol. 2014;45(10):2154–61. doi:10.1016/j.humpath.2014.01.025.

    Article  CAS  PubMed  Google Scholar 

  32. Son J, Lee JH, Kim HN, Ha H, Lee ZH. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction. Biochem Biophys Res Commun. 2010;398(2):309–14. doi:10.1016/j.bbrc.2010.06.087.

    Article  CAS  PubMed  Google Scholar 

  33. Chhabra A, Fernando H, Watkins G, Mansel RE, Jiang WG. Expression of transcription factor CREB1 in human breast cancer and its correlation with prognosis. Oncol Rep. 2007;18(4):953–8.

    CAS  PubMed  Google Scholar 

  34. Zhang M, Xu JJ, Zhou RL, Zhang QY. cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 beta in human breast cancer cells. PLoS ONE. 2013;8(2):e57520. doi:10.1371/journal.pone.0057520.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Resende C, Regalo G, Duraes C, Pinto MT, Wen X, Figueiredo C, et al. Interleukin-1B signalling leads to increased survival of gastric carcinoma cells through a CREB-C/EBPbeta-associated mechanism. Gastric Cancer. 2016;19(1):74–84. doi:10.1007/s10120-014-0448-x.

    Article  CAS  PubMed  Google Scholar 

  36. Wang YW, Chen X, Gao JW, Zhang H, Ma RR, Gao ZH, et al. High expression of cAMP-responsive element-binding protein 1 (CREB1) is associated with metastasis, tumor stage and poor outcome in gastric cancer. Oncotarget. 2015;6(12):10646–57.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Tan X, Wang S, Zhu L, Wu C, Yin B, Zhao J, et al. cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a. Proc Natl Acad Sci U S A. 2012;109(39):15805–10. doi:10.1073/pnas.1207787109.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Yu L, Guo X, Zhang P, Qi R, Li Z, Zhang S. Cyclic adenosine monophosphate-responsive element-binding protein activation predicts an unfavorable prognosis in patients with hepatocellular carcinoma. OncoTargets Ther. 2014;7:873–9. doi:10.2147/ott.s63594.

    Google Scholar 

  39. Dobroff AS, Wang H, Melnikova VO, Villares GJ, Zigler M, Huang L, et al. Silencing cAMP-response element-binding protein (CREB) identifies CYR61 as a tumor suppressor gene in melanoma. J Biol Chem. 2009;284(38):26194–206. doi:10.1074/jbc.M109.019836.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Barresi V, Branca G, Caffo M, Tuccari G. p-CREB expression in human meningiomas: correlation with angiogenesis and recurrence risk. J Neuro-Oncol. 2015;122(1):87–95. doi:10.1007/s11060-014-1706-9.

    Article  CAS  Google Scholar 

  41. Shukla A, Bosenberg MW, MacPherson MB, Butnor KJ, Heintz NH, Pass HI, et al. Activated cAMP response element binding protein is overexpressed in human mesotheliomas and inhibits apoptosis. Am J Pathol. 2009;175(5):2197–206. doi:10.2353/ajpath.2009.090400.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Aggarwal S, Kim SW, Ryu SH, Chung WC, Koo JS. Growth suppression of lung cancer cells by targeting cyclic AMP response element-binding protein. Cancer Res. 2008;68(4):981–8. doi:10.1158/0008-5472.can-06-0249.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Seo HS, Liu DD, Bekele BN, Kim MK, Pisters K, Lippman SM, et al. Cyclic AMP response element-binding protein overexpression: a feature associated with negative prognosis in never smokers with non-small cell lung cancer. Cancer Res. 2008;68(15):6065–73. doi:10.1158/0008-5472.can-07-5376.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Linnerth NM, Greenaway JB, Petrik JJ, Moorehead RA. cAMP response element-binding protein is expressed at high levels in human ovarian adenocarcinoma and regulates ovarian tumor cell proliferation. Int J Gynecol Cancer. 2008;18(6):1248–57. doi:10.1111/j.1525-1438.2007.01177.x.

    Article  CAS  PubMed  Google Scholar 

  45. Wu D, Zhau HE, Huang WC, Iqbal S, Habib FK, Sartor O, et al. cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: implication in human prostate cancer bone metastasis. Oncogene. 2007;26(35):5070–7. doi:10.1038/sj.onc.1210316.

    Article  CAS  PubMed  Google Scholar 

  46. Kumar AP, Bhaskaran S, Ganapathy M, Crosby K, Davis MD, Kochunov P, et al. Akt/cAMP-responsive element binding protein/cyclin D1 network: a novel target for prostate cancer inhibition in transgenic adenocarcinoma of mouse prostate model mediated by nexrutine, a phellodendron amurense bark extract. Clin Cancer Res. 2007;13(9):2784–94. doi:10.1158/1078-0432.ccr-06-2974.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Sakamoto KM, Frank DA. CREB in the pathophysiology of cancer: implications for targeting transcription factors for cancer therapy. Clin Cancer Res. 2009;15(8):2583–7. doi:10.1158/1078-0432.ccr-08-1137.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Barresi V, Mondello S, Branca G, Rajan TS, Vitarelli E, Tuccari G. p-CREB expression in human gliomas: potential use in the differential diagnosis between astrocytoma and oligodendroglioma. Hum Pathol. 2015;46(2):231–8. doi:10.1016/j.humpath.2014.10.011.

    Article  CAS  PubMed  Google Scholar 

  49. Kong WQ, Bai R, Liu T, Cai CL, Liu M, Li X, et al. MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma. FEBS J. 2012;279(7):1252–60. doi:10.1111/j.1742-4658.2012.08519.x.

    Article  CAS  PubMed  Google Scholar 

  50. Perry C, Sklan EH, Soreq H. CREB regulates AChE-R-induced proliferation of human glioblastoma cells. Neoplasia (New York, NY). 2004;6(3):279–86. doi:10.1593/neo.3424.

    Article  CAS  Google Scholar 

  51. Dai N, Zhong ZY, Cun YP, Qing Y, Chen C, Jiang P, et al. Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA. Neoplasma. 2013;60(4):384–94. doi:10.4149/neo_2013_050.

    Article  CAS  PubMed  Google Scholar 

  52. Polytarchou C, Iliopoulos D, Hatziapostolou M, Kottakis F, Maroulakou I, Struhl K, et al. Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res. 2011;71(13):4720–31. doi:10.1158/0008-5472.can-11-0365.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Li QQ, Zhang L, Wan HY, Liu M, Li X, Tang H. CREB1-driven expression of miR-320a promotes mitophagy by down-regulating VDAC1 expression during serum starvation in cervical cancer cells. Oncotarget. 2015. doi:10.18632/oncotarget.5318.

    Google Scholar 

  54. Martin NT, Nakamura K, Davies R, Nahas SA, Brown C, Tunuguntla R, et al. ATM-dependent MiR-335 targets CtIP and modulates the DNA damage response. PLoS Genet. 2013;9(5):e1003505. doi:10.1371/journal.pgen.1003505.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Wendler A, Keller D, Albrecht C, Peluso JJ, Wehling M. Involvement of let-7/miR-98 microRNAs in the regulation of progesterone receptor membrane component 1 expression in ovarian cancer cells. Oncol Rep. 2011;25(1):273–9.

    CAS  PubMed  Google Scholar 

  56. Zhao Y, Deng C, Lu W, **ao J, Ma D, Guo M, et al. let-7 microRNAs induce tamoxifen sensitivity by downregulation of estrogen receptor alpha signaling in breast cancer. Mol Med (Cambridge, Mass). 2011;17(11–12):1233–41. doi:10.2119/molmed.2010.00225.

    CAS  Google Scholar 

  57. Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, et al. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 2008;68(24):10307–14. doi:10.1158/0008-5472.can-08-1954.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Tian Y, Hao S, Ye M, Zhang A, Nan Y, Wang G, et al. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly. Biochem Biophys Res Commun. 2015;458(2):307–12. doi:10.1016/j.bbrc.2015.01.105.

    Article  CAS  PubMed  Google Scholar 

  59. Zhang P, Ma Y, Wang F, Yang J, Liu Z, Peng J, et al. Comprehensive gene and microRNA expression profiling reveals the crucial role of hsa-let-7i and its target genes in colorectal cancer metastasis. Mol Biol Rep. 2012;39(2):1471–8. doi:10.1007/s11033-011-0884-1.

    Article  PubMed  CAS  Google Scholar 

  60. Hur K, Toiyama Y, Schetter AJ, Okugawa Y, Harris CC, Boland CR, et al. Identification of a metastasis-specific microRNA signature in human colorectal cancer. J Natl Cancer Inst. 2015;107(3):dju492. doi:10.1093/jnci/dju492.

    Article  PubMed Central  PubMed  Google Scholar 

  61. Subramanian M, Francis P, Bilke S, Li XL, Hara T, Lu X, et al. A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis. Oncogene. 2015;34(9):1094–104. doi:10.1038/onc.2014.46.

    Article  CAS  PubMed  Google Scholar 

  62. Wang H, Zhang W, Zuo Y, Ding M, Ke C, Yan R, et al. miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer. Tumour Biol. 2015. doi:10.1007/s13277-015-3713-7.

    Google Scholar 

  63. **e D, Shang C, Zhang H, Guo Y, Tong X. Up-regulation of miR-9 target CBX7 to regulate invasion ability of bladder transitional cell carcinoma. Med Sci Monit. 2015;21:225–30. doi:10.12659/msm.893232.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Drakaki A, Hatziapostolou M, Polytarchou C, Vorvis C, Poultsides GA, Souglakos J, et al. Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway. BMC Cancer. 2015;15:542. doi:10.1186/s12885-015-1562-9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Cai L, Cai X. Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma. Diagn Pathol. 2014;9:1000. doi:10.1186/s13000-014-0228-2.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Higashi T, Hayashi H, Ishimoto T, Takeyama H, Kaida T, Arima K, et al. miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells. Br J Cancer. 2015;113(2):252–8. doi:10.1038/bjc.2015.170.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Pan X, Wang ZX, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther. 2010;10(12):1224–32.

    Article  CAS  PubMed  Google Scholar 

  68. Wang W, Li J, Zhu W, Gao C, Jiang R, Li W, et al. MicroRNA-21 and the clinical outcomes of various carcinomas: a systematic review and meta-analysis. BMC Cancer. 2014;14:819. doi:10.1186/1471-2407-14-819.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature. 2010;467(7311):86–90. doi: http://www.nature.com/nature/journal/v467/n7311/abs/nature09284.html#supplementary-information .

    Article  CAS  PubMed  Google Scholar 

  70. Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009;13(1):39–53. doi:10.1111/j.1582-4934.2008.00556.x.

    Article  CAS  PubMed  Google Scholar 

  71. Fujita S, Ito T, Mizutani T, Minoguchi S, Yamamichi N, Sakurai K, et al. miR-21 gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol. 2008;378(3):492–504. doi:10.1016/j.jmb.2008.03.015.

    Article  CAS  PubMed  Google Scholar 

  72. Zheng H, Li W, Wang Y, **e T, Cai Y, Wang Z, et al. miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer. Carcinogenesis. 2014;35(1):173–83. doi:10.1093/carcin/bgt274.

    Article  CAS  PubMed  Google Scholar 

  73. Ma G, Dai W, Sang A, Yang X, Gao C. Upregulation of microRNA-23a/b promotes tumor progression and confers poor prognosis in patients with gastric cancer. Int J Clin Exp Pathol. 2014;7(12):8833–40.

    PubMed Central  PubMed  Google Scholar 

  74. Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, et al. MiR-23a regulates TGF-beta-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol. 2012;41(3):869–75. doi:10.3892/ijo.2012.1535.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Cao M, Li Y, Lu H, Meng Q, Wang L, Cai L, et al. MiR-23a-mediated migration/invasion is rescued by its target, IRS-1, in non-small cell lung cancer cells. J Cancer Res Clin Oncol. 2014;140(10):1661–70. doi:10.1007/s00432-014-1725-0.

    Article  CAS  PubMed  Google Scholar 

  76. Cai S, Chen R, Li X, Cai Y, Ye Z, Li S, et al. Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway. Oncotarget. 2015;6(6):3904–17.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Macartney-Coxson DP, Hood KA, Shi HJ, Ward T, Wiles A, O’Connor R, et al. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level. BMC Cancer. 2008;8:187. doi:10.1186/1471-2407-8-187.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Knosel T, Schluns K, Stein U, Schwabe H, Schlag PM, Dietel M, et al. Chromosomal alterations during lymphatic and liver metastasis formation of colorectal cancer. Neoplasia (New York, NY). 2004;6(1):23–8.

    Article  Google Scholar 

  79. Huang A, Zhao H, Quan Y, ** R, Feng B, Zheng M. E2A predicts prognosis of colorectal cancer patients and regulates cancer cell growth by targeting miR-320a. PLoS ONE. 2014;9(1):e85201. doi:10.1371/journal.pone.0085201.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  80. Salendo J, Spitzner M, Kramer F, Zhang X, Jo P, Wolff HA, et al. Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a, −224, −132 and let7g. Radiother Oncol. 2013;108(3):451–7. doi:10.1016/j.radonc.2013.06.032.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang Y, He X, Liu Y, Ye Y, Zhang H, He P, et al. MicroRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer. Oncol Rep. 2012;27(3):685–94. doi:10.3892/or.2011.1561.

    CAS  PubMed  Google Scholar 

  82. Sun JY, Huang Y, Li JP, Zhang X, Wang L, Meng YL, et al. MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting beta-catenin. Biochem Biophys Res Commun. 2012;420(4):787–92. doi:10.1016/j.bbrc.2012.03.075.

    Article  CAS  PubMed  Google Scholar 

  83. Zhao H, Dong T, Zhou H, Wang L, Huang A, Feng B, et al. miR-320a suppresses colorectal cancer progression by targeting Rac1. Carcinogenesis. 2014;35(4):886–95. doi:10.1093/carcin/bgt378.

    Article  CAS  PubMed  Google Scholar 

  84. Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, Dyrskjot L, et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 2008;68(15):6416–24. doi:10.1158/0008-5472.can-07-6110.

    Article  CAS  PubMed  Google Scholar 

  85. **shan Z, Ziying L, **g D, Gang L. MicroRNA-320a acts as a tumor suppressor by targeting BCR/ABL oncogene in chronic myeloid leukemia. Sci Rep. 2015;5:12460. doi:10.1038/srep12460.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Qi X, Li J, Zhou C, Lv C, Tian M. MicroRNA-320a inhibits cell proliferation, migration and invasion by targeting BMI-1 in nasopharyngeal carcinoma. FEBS Lett. 2014;588(20):3732–8. doi:10.1016/j.febslet.2014.08.021.

    Article  CAS  PubMed  Google Scholar 

  87. Yao J, Liang LH, Zhang Y, Ding J, Tian Q, Li JJ, et al. GNAI1 suppresses tumor cell migration and invasion and is post-transcriptionally regulated by Mir-320a/c/d in hepatocellular carcinoma. Cancer Biol Med. 2012;9(4):234–41. doi:10.7497/j.issn.2095-3941.2012.04.003.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Guo T, Feng Y, Liu Q, Yang X, Jiang T, Chen Y, et al. MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R. Tumour Biol. 2014;35(11):11269–75. doi:10.1007/s13277-014-2283-4.

    Article  CAS  PubMed  Google Scholar 

  89. Sun L, Liu B, Lin Z, Yao Y, Chen Y, Li Y, et al. MiR-320a acts as a prognostic factor and inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3. Mol Cancer. 2015;14:96. doi:10.1186/s12943-015-0344-y.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Shang C, Zhang H, Guo Y, Hong Y, Liu Y, Xue Y. MiR-320a down-regulation mediates bladder carcinoma invasion by targeting ITGB3. Mol Biol Rep. 2014;41(4):2521–7. doi:10.1007/s11033-014-3110-0.

    Article  CAS  PubMed  Google Scholar 

  91. Li H, **e S, Liu M, Chen Z, Liu X, Wang L, et al. The clinical significance of downregulation of mir-124-3p, mir-146a-5p, mir-155-5p and mir-335-5p in gastric cancer tumorigenesis. Int J Oncol. 2014;45(1):197–208. doi:10.3892/ijo.2014.2415.

    CAS  PubMed  Google Scholar 

  92. Wang H, Li M, Zhang R, Wang Y, Zang W, Ma Y, et al. Effect of miR-335 upregulation on the apoptosis and invasion of lung cancer cell A549 and H1299. Tumour Biol. 2013;34(5):3101–9. doi:10.1007/s13277-013-0878-9.

    Article  CAS  PubMed  Google Scholar 

  93. Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, et al. Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. Int J Oncol. 2013;42(2):411–8. doi:10.3892/ijo.2012.1724.

    CAS  PubMed  Google Scholar 

  94. Yan Z, **ong Y, Xu W, Gao J, Cheng Y, Wang Z, et al. Identification of hsa-miR-335 as a prognostic signature in gastric cancer. PLoS ONE. 2012;7(7):e40037. doi:10.1371/journal.pone.0040037.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Lynch J, Meehan MH, Crean J, Copeland J, Stallings RL, Bray IM. Metastasis suppressor microRNA-335 targets the formin family of actin nucleators. PLoS ONE. 2013;8(11):e78428. doi:10.1371/journal.pone.0078428.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Li Z, Li D, Zhang G, **ong J, Jie Z, Cheng H, et al. Methylation-associated silencing of MicroRNA-335 contributes tumor cell invasion and migration by interacting with RASA1 in gastric cancer. Am J Cancer Res. 2014;4(6):648–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  97. **ong SW, Lin TX, Xu KW, Dong W, Ling XH, Jiang FN, et al. MicroRNA-335 acts as a candidate tumor suppressor in prostate cancer. Pathol Oncol Res. 2013;19(3):529–37. doi:10.1007/s12253-013-9613-5.

    Article  CAS  PubMed  Google Scholar 

  98. Meng Y, Zou Q, Liu T, Cai X, Huang Y, Pan J. MicroRNA-335 inhibits proliferation, cell-cycle progression, colony formation, and invasion via targeting PAX6 in breast cancer cells. Molecular Med Rep. 2015;11(1):379–85. doi:10.3892/mmr.2014.2684.

    CAS  Google Scholar 

  99. Wang C, Jiang T. MicroRNA-335 represents an independent prognostic marker in cervical cancer. Tumour Biol. 2015. doi:10.1007/s13277-015-3252-2.

    Google Scholar 

  100. Qiao J, Lee S, Paul P, Theiss L, Tiao J, Qiao L, et al. miR-335 and miR-363 regulation of neuroblastoma tumorigenesis and metastasis. Surgery. 2013;154(2):226–33. doi:10.1016/j.surg.2013.04.005.

    Article  PubMed Central  PubMed  Google Scholar 

  101. Gao L, Yang Y, Xu H, Liu R, Li D, Hong H, et al. MiR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4. Tumour Biol. 2014;35(8):8309–18. doi:10.1007/s13277-014-2092-9.

    Article  CAS  PubMed  Google Scholar 

  102. Gao Y, Zeng F, Wu JY, Li HY, Fan JJ, Mai L, et al. MiR-335 inhibits migration of breast cancer cells through targeting oncoprotein c-Met. Tumour Biol. 2015;36(4):2875–83. doi:10.1007/s13277-014-2917-6.

    Article  CAS  PubMed  Google Scholar 

  103. Gong M, Ma J, Guillemette R, Zhou M, Yang Y, Yang Y, et al. miR-335 inhibits small cell lung cancer bone metastases via IGF-IR and RANKL pathways. Mol Cancer Res. 2014;12(1):101–10. doi:10.1158/1541-7786.mcr-13-0136.

    Article  CAS  PubMed  Google Scholar 

  104. Wang K, Chen X, Zhan Y, Jiang W, Liu X, Wang X, et al. miR-335 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells through direct suppression of BCL-W. Tumour Biol. 2015. doi:10.1007/s13277-015-3382-6.

    Google Scholar 

  105. Shi L, Jiang D, Sun G, Wan Y, Zhang S, Zeng Y, et al. miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas. J Neuro-Oncol. 2012;110(2):155–62. doi:10.1007/s11060-012-0951-z.

    Article  CAS  Google Scholar 

  106. Cao J, Cai J, Huang D, Han Q, Yang Q, Li T, et al. miR-335 represents an invasion suppressor gene in ovarian cancer by targeting Bcl-w. Oncol Rep. 2013;30(2):701–6. doi:10.3892/or.2013.2482.

    CAS  PubMed  Google Scholar 

  107. Wang Y, Zhao W, Fu Q. miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 2013;384(1–2):105–11. doi:10.1007/s11010-013-1786-4.

    Article  CAS  PubMed  Google Scholar 

  108. Heidary MF, Mahmoodzadeh Hosseini H, Mehdizadeh Aghdam E, Nourani MR, Ranjbar R, Mirnejad R, et al. Overexpression of metastatic related microRNAs, Mir-335 and Mir-10b, by staphylococcal enterotoxin B in the metastatic breast cancer cell line. Adv Pharma Bull. 2015;5(2):255–9. doi:10.15171/apb.2015.035.

    Article  Google Scholar 

  109. Cheng Q, Cao H, Chen Z, Ma Z, Wan X, Peng R, et al. PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells. Mol Med Rep. 2014;10(1):399–404. doi:10.3892/mmr.2014.2150.

    CAS  PubMed  Google Scholar 

  110. Zhang BJ, Gong HY, Zheng F, Liu DJ, Liu HX. Up-regulation of miR-335 predicts a favorable prognosis in esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7(9):6213–8.

    PubMed Central  PubMed  Google Scholar 

  111. Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006;124(6):1169–81. doi:10.1016/j.cell.2006.02.037.

    Article  CAS  PubMed  Google Scholar 

  112. Suh MR, Lee Y, Kim JY, Kim SK, Moon SH, Lee JY, et al. Human embryonic stem cells express a unique set of microRNAs. Dev Biol. 2004;270(2):488–98. doi:10.1016/j.ydbio.2004.02.019.

    Article  CAS  PubMed  Google Scholar 

  113. Wei F, Cao C, Xu X, Wang J. Diverse functions of miR-373 in cancer. J Transl Med. 2015;13:162. doi:10.1186/s12967-015-0523-z.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  114. Adi Harel S, Bossel Ben-Moshe N, Aylon Y, Bublik DR, Moskovits N, Toperoff G, et al. Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung cancer cells to cisplatin and restricts tumor growth. Cell Death Differ. 2015;22(8):1328–40. doi:10.1038/cdd.2014.221.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Attar M, Arefian E, Nabiuni M, Adegani FJ, Bakhtiari SH, Karimi Z, et al. MicroRNA 17–92 expressed by a transposone-based vector changes expression level of cell-cycle-related genes. Cell Biol Int. 2012;36(11):1005–12. doi:10.1042/cbi20110089.

    Article  CAS  PubMed  Google Scholar 

  116. Pigazzi M, Manara E, Baron E, Basso G. miR-34b targets cyclic AMP-responsive element binding protein in acute myeloid leukemia. Cancer Res. 2009;69(6):2471–8. doi:10.1158/0008-5472.can-08-3404.

    Article  CAS  PubMed  Google Scholar 

  117. Pigazzi M, Manara E, Bresolin S, Tregnago C, Beghin A, Baron E, et al. MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation. Haematologica. 2013;98(4):602–10. doi:10.3324/haematol.2012.070664.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Chen L, Yang Q, Kong WQ, Liu T, Liu M, Li X, et al. MicroRNA-181b targets cAMP responsive element binding protein 1 in gastric adenocarcinomas. IUBMB life. 2012;64(7):628–35. doi:10.1002/iub.1030.

    Article  CAS  PubMed  Google Scholar 

  119. Peng B, Hu S, Jun Q, Luo D, Zhang X, Zhao H, et al. MicroRNA-200b targets CREB1 and suppresses cell growth in human malignant glioma. Mol Cell Biochem. 2013;379(1–2):51–8. doi:10.1007/s11010-013-1626-6.

    Article  CAS  PubMed  Google Scholar 

  120. Noguchi S, Kumazaki M, Yasui Y, Mori T, Yamada N, Akao Y. MicroRNA-203 regulates melanosome transport and tyrosinase expression in melanoma cells by targeting kinesin superfamily protein 5b. J Investig Dermatol. 2014;134(2):461–9. doi:10.1038/jid.2013.310.

    Article  CAS  PubMed  Google Scholar 

  121. Wong KY, Liang R, So CC, ** DY, Costello JF, Chim CS. Epigenetic silencing of MIR203 in multiple myeloma. Br J Haematol. 2011;154(5):569–78. doi:10.1111/j.1365-2141.2011.08782.x.

    Article  CAS  PubMed  Google Scholar 

  122. Noguchi S, Kumazaki M, Mori T, Baba K, Okuda M, Mizuno T, et al. Analysis of microRNA-203 function in CREB/MITF/RAB27a pathway: comparison between canine and human melanoma cells. Vet Comp Oncol. 2014. doi:10.1111/vco.12118.

    Google Scholar 

  123. Yang Z, Tsuchiya H, Zhang Y, Hartnett ME, Wang L. MicroRNA-433 inhibits liver cancer cell migration by repressing the protein expression and function of cAMP response element-binding protein. J Biol Chem. 2013;288(40):28893–9. doi:10.1074/jbc.M113.502682.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  124. Olive V, Jiang I, He L. mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol. 2010;42(8):1348–54. doi:10.1016/j.biocel.2010.03.004.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  125. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435(7043):828–33. doi:10.1038/nature03552.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  126. ** L, Wessely O, Marcusson EG, Ivan C, Calin GA, Alahari SK. Prooncogenic factors miR-23b and miR-27b are regulated by Her2/Neu, EGF, and TNF-alpha in breast cancer. Cancer Res. 2013;73(9):2884–96. doi:10.1158/0008-5472.can-12-2162.

    Article  CAS  PubMed  Google Scholar 

  127. Chiyomaru T, Seki N, Inoguchi S, Ishihara T, Mataki H, Matsushita R, et al. Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer. Int J Oncol. 2015;46(2):487–96. doi:10.3892/ijo.2014.2752.

    CAS  PubMed  Google Scholar 

  128. Goto Y, Kojima S, Nishikawa R, Enokida H, Chiyomaru T, Kinoshita T, et al. The microRNA-23b/27b/24-1 cluster is a disease progression marker and tumor suppressor in prostate cancer. Oncotarget. 2014;5(17):7748–59.

    Article  PubMed Central  PubMed  Google Scholar 

  129. Ishteiwy RA, Ward TM, Dykxhoorn DM, Burnstein KL. The microRNA -23b/-27b cluster suppresses the metastatic phenotype of castration-resistant prostate cancer cells. PLoS ONE. 2012;7(12):e52106. doi:10.1371/journal.pone.0052106.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  130. Jiang J, Lv X, Fan L, Huang G, Zhan Y, Wang M, et al. MicroRNA-27b suppresses growth and invasion of NSCLC cells by targeting Sp1. Tumour Biol. 2014;35(10):10019–23. doi:10.1007/s13277-014-2294-1.

    Article  CAS  PubMed  Google Scholar 

  131. Wan L, Zhang L, Fan K, Wang J. MiR-27b targets LIMK1 to inhibit growth and invasion of NSCLC cells. Mol Cell Biochem. 2014;390(1–2):85–91. doi:10.1007/s11010-013-1959-1.

    Article  CAS  PubMed  Google Scholar 

  132. Mu W, Hu C, Zhang H, Qu Z, Cen J, Qiu Z, et al. miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression. Cell Res. 2015;25(4):477–95. doi:10.1038/cr.2015.23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  133. Zhang S, Liu F, Mao X, Huang J, Yang J, Yin X, et al. Elevation of miR-27b by HPV16 E7 inhibits PPARgamma expression and promotes proliferation and invasion in cervical carcinoma cells. Int J Oncol. 2015. doi:10.3892/ijo.2015.3162.

    Google Scholar 

  134. Chen L, Li H, Han L, Zhang K, Wang G, Wang Y, et al. Expression and function of miR-27b in human glioma. Oncol Rep. 2011;26(6):1617–21. doi:10.3892/or.2011.1458.

    CAS  PubMed  Google Scholar 

  135. Wang Y, Rathinam R, Walch A, Alahari SK. ST14 (suppression of tumorigenicity 14) gene is a target for miR-27b, and the inhibitory effect of ST14 on cell growth is independent of miR-27b regulation. J Biol Chem. 2009;284(34):23094–106. doi:10.1074/jbc.M109.012617.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  136. Zhu Y, Zhang X, Ding X, Wang H, Chen X, Zhao H, et al. miR-27 inhibits adipocyte differentiation via suppressing CREB expression. Acta Biochim Biophys Sin. 2014;46(7):590–6. doi:10.1093/abbs/gmu036.

    Article  CAS  PubMed  Google Scholar 

  137. Chien CH, Sun YM, Chang WC, Chiang-Hsieh PY, Lee TY, Tsai WC, et al. Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data. Nucleic Acids Res. 2011;39(21):9345–56. doi:10.1093/nar/gkr604.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  138. Chang TH, Huang HY, Hsu JB, Weng SL, Horng JT, Huang HD. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinforma. 2013;14 Suppl 2:S4. doi:10.1186/1471-2105-14-s2-s4.

    CAS  Google Scholar 

  139. Messeguer X, Escudero R, Farre D, Nunez O, Martinez J, Alba MM. PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics (Oxford, Engl). 2002;18(2):333–4.

    Article  CAS  Google Scholar 

  140. Fabbri M, Croce CM, Calin GA. MicroRNAs. Cancer J (Sudbury, Mass). 2008;14(1):1–6. doi:10.1097/PPO.0b013e318164145e.

    Article  CAS  Google Scholar 

  141. He L, He X, Lowe SW, Hannon GJ. MicroRNAs join the p53 network—another piece in the tumour-suppression puzzle. Nat Rev Cancer. 2007;7(11):819–22. doi:10.1038/nrc2232.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  142. Hiyoshi Y, Schetter AJ, Okayama H, Inamura K, Anami K, Nguyen GH, et al. Increased microRNA-34b and -34c predominantly expressed in stromal tissues is associated with poor prognosis in human colon cancer. PLoS ONE. 2015;10(4):e0124899. doi:10.1371/journal.pone.0124899.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  143. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68(11):4123–32. doi:10.1158/0008-5472.can-08-0325.

    Article  CAS  PubMed  Google Scholar 

  144. Suzuki H, Yamamoto E, Nojima M, Kai M, Yamano HO, Yoshikawa K, et al. Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. Carcinogenesis. 2010;31(12):2066–73. doi:10.1093/carcin/bgq203.

    Article  CAS  PubMed  Google Scholar 

  145. Forno I, Ferrero S, Russo MV, Gazzano G, Giangiobbe S, Montanari E, et al. Deregulation of MiR-34b/Sox2 predicts prostate cancer progression. PLoS ONE. 2015;10(6):e0130060. doi:10.1371/journal.pone.0130060.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  146. Majid S, Dar AA, Saini S, Shahryari V, Arora S, Zaman MS, et al. miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways. Clin Cancer Res. 2013;19(1):73–84. doi:10.1158/1078-0432.ccr-12-2952.

    Article  CAS  PubMed  Google Scholar 

  147. **e K, Liu J, Chen J, Dong J, Ma H, Liu Y, et al. Methylation-associated silencing of microRNA-34b in hepatocellular carcinoma cancer. Gene. 2014;543(1):101–7. doi:10.1016/j.gene.2014.03.059.

    Article  CAS  PubMed  Google Scholar 

  148. Wang LG, Ni Y, Su BH, Mu XR, Shen HC, Du JJ. MicroRNA-34b functions as a tumor suppressor and acts as a nodal point in the feedback loop with Met. Int J Oncol. 2013;42(3):957–62. doi:10.3892/ijo.2013.1767.

    CAS  PubMed  Google Scholar 

  149. Liu C, Cheng H, Shi S, Cui X, Yang J, Chen L, et al. MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3. Curr Mol Med. 2013;13(4):467–78.

    Article  CAS  PubMed  Google Scholar 

  150. Liu X, Feng J, Tang L, Liao L, Xu Q, Zhu S. The regulation and function of miR-21-FOXO3a-miR-34b/c signaling in breast cancer. Int J Mol Sci. 2015;16(2):3148–62. doi:10.3390/ijms16023148.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  151. Corney DC, Hwang CI, Matoso A, Vogt M, Flesken-Nikitin A, Godwin AK, et al. Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res. 2010;16(4):1119–28. doi:10.1158/1078-0432.ccr-09-2642.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  152. Liu G, Min H, Yue S, Chen CZ. Pre-miRNA loop nucleotides control the distinct activities of mir-181a-1 and mir-181c in early T cell development. PLoS ONE. 2008;3(10):e3592. doi:10.1371/journal.pone.0003592.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  153. Liu J, Shi W, Wu C, Ju J, Jiang J. miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (review). BioMed Rep. 2014;2(1):7–11. doi:10.3892/br.2013.199.

    CAS  PubMed  Google Scholar 

  154. Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 2010;39(4):493–506. doi:10.1016/j.molcel.2010.07.023.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  155. Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, et al. MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation. J Clin Invest. 2012;122(6):1973–90. doi:10.1172/jci61495.

    CAS  PubMed Central  PubMed  Google Scholar 

  156. **a Y, Gao Y. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2. Biochem Biophys Res Commun. 2014;447(3):446–51. doi:10.1016/j.bbrc.2014.04.027.

    Article  CAS  PubMed  Google Scholar 

  157. Panarelli NC, Chen YT, Zhou XK, Kitabayashi N, Yantiss RK. MicroRNA expression aids the preoperative diagnosis of pancreatic ductal adenocarcinoma. Pancreas. 2012;41(5):685–90. doi:10.1097/MPA.0b013e318243a905.

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Nurul-Syakima AM, Yoke-Kqueen C, Sabariah AR, Shiran MS, Singh A, Learn-Han L. Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers. Int J Mol Med. 2011;28(3):327–36. doi:10.3892/ijmm.2011.714.

    PubMed  Google Scholar 

  159. Ratert N, Meyer HA, Jung M, Mollenkopf HJ, Wagner I, Miller K, et al. Reference miRNAs for miRNAome analysis of urothelial carcinomas. PLoS ONE. 2012;7(6):e39309. doi:10.1371/journal.pone.0039309.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  160. Li D, Jian W, Wei C, Song H, Gu Y, Luo Y, et al. Down-regulation of miR-181b promotes apoptosis by targeting CYLD in thyroid papillary cancer. Int J Clin Exp Pathol. 2014;7(11):7672–80.

    PubMed Central  PubMed  Google Scholar 

  161. Sun YC, Wang J, Guo CC, Sai K, Wang J, Chen FR, et al. MiR-181b sensitizes glioma cells to teniposide by targeting MDM2. BMC Cancer. 2014;14:611. doi:10.1186/1471-2407-14-611.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  162. Shi ZM, Wang XF, Qian X, Tao T, Wang L, Chen QD, et al. MiRNA-181b suppresses IGF-1R and functions as a tumor suppressor gene in gliomas. RNA (New York, NY). 2013;19(4):552–60. doi:10.1261/rna.035972.112.

    Article  CAS  Google Scholar 

  163. Zhi F, Wang Q, Deng D, Shao N, Wang R, Xue L, et al. MiR-181b-5p downregulates NOVA1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma. PLoS ONE. 2014;9(10):e109124. doi:10.1371/journal.pone.0109124.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  164. Lu F, Zhang J, Ji M, Li P, Du Y, Wang H, et al. miR-181b increases drug sensitivity in acute myeloid leukemia via targeting HMGB1 and Mcl-1. Int J Oncol. 2014;45(1):383–92. doi:10.3892/ijo.2014.2390.

    CAS  PubMed  Google Scholar 

  165. Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, et al. Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 2010;126(5):1166–76. doi:10.1002/ijc.24827.

    CAS  PubMed  Google Scholar 

  166. Guo JX, Tao QS, Lou PR, Chen XC, Chen J, Yuan GB. miR-181b as a potential molecular target for anticancer therapy of gastric neoplasms. Asian Pac J Cancer Prev. 2012;13(5):2263–7.

    Article  PubMed  Google Scholar 

  167. Tang X, Zheng D, Hu P, Zeng Z, Li M, Tucker L, et al. Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the beta-catenin/TCF/LEF-1 pathway in gastric cancer cells. Nucleic Acids Res. 2014;42(5):2988–98. doi:10.1093/nar/gkt1275.

    Article  CAS  PubMed  Google Scholar 

  168. Zhang QH, Sun HM, Zheng RZ, Li YC, Zhang Q, Cheng P, et al. Meta-analysis of microRNA-183 family expression in human cancer studies comparing cancer tissues with noncancerous tissues. Gene. 2013;527(1):26–32. doi:10.1016/j.gene.2013.06.006.

    Article  CAS  PubMed  Google Scholar 

  169. Zhu YJ, Xu B, **a W. Hsa-mir-182 downregulates RASA1 and suppresses lung squamous cell carcinoma cell proliferation. Clin Lab. 2014;60(1):155–9.

    CAS  PubMed  Google Scholar 

  170. Li Y, Zhang D, Wang X, Yao X, Ye C, Zhang S, et al. Hypoxia-inducible miR-182 enhances HIF1alpha signaling via targeting PHD2 and FIH1 in prostate cancer. Sci Rep. 2015;5:12495. doi:10.1038/srep12495.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  171. Du C, Weng X, Hu W, Lv Z, **ao H, Ding C, et al. Hypoxia-inducible MiR-182 promotes angiogenesis by targeting RASA1 in hepatocellular carcinoma. J Exp Clin Cancer Res. 2015;34(1):67. doi:10.1186/s13046-015-0182-1.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  172. Sachdeva M, Mito JK, Lee CL, Zhang M, Li Z, Dodd RD, et al. MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes. J Clin Invest. 2014;124(10):4305–19. doi:10.1172/jci77116.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  173. Ning FL, Wang F, Li ML, Yu ZS, Hao YZ, Chen SS. MicroRNA-182 modulates chemosensitivity of human non-small cell lung cancer to cisplatin by targeting PDCD4. Diagn Pathol. 2014;9:143. doi:10.1186/1746-1596-9-143.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  174. Kouri FM, Hurley LA, Daniel WL, Day ES, Hua Y, Hao L, et al. miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma. Genes Dev. 2015;29(7):732–45. doi:10.1101/gad.257394.114.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  175. Zhang Y, Wang X, Wang Z, Tang H, Fan H, Guo Q. miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer. Oncol Rep. 2015;33(5):2592–8. doi:10.3892/or.2015.3833.

    CAS  PubMed  Google Scholar 

  176. Zhu H, Fang J, Zhang J, Zhao Z, Liu L, Wang J, et al. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma. Biochem Biophys Res Commun. 2014;450(1):857–62. doi:10.1016/j.bbrc.2014.06.073.

    Article  CAS  PubMed  Google Scholar 

  177. Wang C, Ren R, Hu H, Tan C, Han M, Wang X, et al. MiR-182 is up-regulated and targeting Cebpa in hepatocellular carcinoma. Chin J Cancer Res. 2014;26(1):17–29. doi:10.3978/j.issn.1000-9604.2014.01.01.

    CAS  PubMed Central  PubMed  Google Scholar 

  178. Tang L, Chen F, Pang EJ, Zhang ZQ, ** BW, Dong WF. MicroRNA-182 inhibits proliferation through targeting oncogenic ANUBL1 in gastric cancer. Oncol Rep. 2015;33(4):1707–16. doi:10.3892/or.2015.3798.

    CAS  PubMed  Google Scholar 

  179. Li X, Luo F, Li Q, Xu M, Feng D, Zhang G, et al. Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance. Oncol Rep. 2011;26(6):1431–9. doi:10.3892/or.2011.1437.

    PubMed  Google Scholar 

  180. Feng B, Wang R, Chen LB. Review of miR-200b and cancer chemosensitivity. Biomed Pharmacother. 2012;66(6):397–402. doi:10.1016/j.biopha.2012.06.002.

    Article  CAS  PubMed  Google Scholar 

  181. Mongroo PS, Rustgi AK. The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther. 2010;10(3):219–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  182. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601. doi:10.1038/ncb1722.

    Article  CAS  PubMed  Google Scholar 

  183. Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008;68(19):7846–54. doi:10.1158/0008-5472.can-08-1942.

    Article  CAS  PubMed  Google Scholar 

  184. Wu H, Wang G, Wang Z, An S, Ye P, Luo S. A negative feedback loop between miR-200b and the NF-kappaB pathway via IKBKB/IKK-beta in breast cancer cells. FEBS J. 2015. doi:10.1111/febs.13543.

    PubMed Central  Google Scholar 

  185. Imaoka H, Toiyama Y, Okigami M, Yasuda H, Saigusa S, Ohi M, et al. Circulating microRNA-203 predicts metastases, early recurrence, and poor prognosis in human gastric cancer. Gastric Cancer. 2015. doi:10.1007/s10120-015-0521-0.

    PubMed  Google Scholar 

  186. Zhou X, Xu G, Yin C, ** W, Zhang G. Down-regulation of miR-203 induced by helicobacter pylori infection promotes the proliferation and invasion of gastric cancer by targeting CASK. Oncotarget. 2014;5(22):11631–40.

    Article  PubMed Central  PubMed  Google Scholar 

  187. Siu MK, Abou-Kheir W, Yin JJ, Chang YS, Barrett B, Suau F, et al. Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. Oncotarget. 2014;5(11):3770–84.

    Article  PubMed Central  PubMed  Google Scholar 

  188. Liao H, Bai Y, Qiu S, Zheng L, Huang L, Liu T, et al. MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2. Oncotarget. 2015;6(11):8914–28.

    Article  PubMed Central  PubMed  Google Scholar 

  189. Shi Y, Tan YJ, Zeng DZ, Qian F, Yu PW. miR-203 suppression in gastric carcinoma promotes slug-mediated cancer metastasis. Tumour Biol. 2015. doi:10.1007/s13277-015-3765-8.

    PubMed Central  Google Scholar 

  190. Chen T, Xu C, Chen J, Ding C, Xu Z, Li C, et al. MicroRNA-203 inhibits cellular proliferation and invasion by targeting Bmi1 in non-small cell lung cancer. Oncol Lett. 2015;9(6):2639–46. doi:10.3892/ol.2015.3080.

    PubMed Central  PubMed  Google Scholar 

  191. Mine M, Yamaguchi K, Sugiura T, Chigita S, Yoshihama N, Yoshihama R, et al. miR-203 inhibits frizzled-2 expression via CD82/KAI1 expression in human lung carcinoma cells. PLoS ONE. 2015;10(7):e0131350. doi:10.1371/journal.pone.0131350.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  192. Wang N, Liang H, Zhou Y, Wang C, Zhang S, Pan Y, et al. miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC. PLoS ONE. 2014;9(8):e105570. doi:10.1371/journal.pone.0105570.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  193. Li T, Gao F, Zhang XP. miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncol Rep. 2015;33(2):607–14. doi:10.3892/or.2014.3646.

    CAS  PubMed  Google Scholar 

  194. Li Z, Du L, Dong Z, Yang Y, Zhang X, Wang L, et al. MiR-203 suppresses ZNF217 upregulation in colorectal cancer and its oncogenicity. PLoS ONE. 2015;10(1):e0116170. doi:10.1371/journal.pone.0116170.

    Article  PubMed Central  PubMed  Google Scholar 

  195. Weiner-Gorzel K, Dempsey E, Milewska M, McGoldrick A, Toh V, Walsh A, et al. Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells. Cancer Med. 2015;4(5):745–58. doi:10.1002/cam4.409.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  196. Furlong F, Fitzpatrick P, O’Toole S, Phelan S, McGrogan B, Maguire A, et al. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer. J Pathol. 2012;226(5):746–55. doi:10.1002/path.3035.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  197. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11(2):136–46. doi:10.1016/s1470-2045(09)70343-2.

    Article  CAS  PubMed  Google Scholar 

  198. Lin X, Rice KL, Buzzai M, Hexner E, Costa FF, Kilpivaara O, et al. miR-433 is aberrantly expressed in myeloproliferative neoplasms and suppresses hematopoietic cell growth and differentiation. Leukemia. 2013;27(2):344–52. doi:10.1038/leu.2012.224.

    Article  CAS  PubMed  Google Scholar 

  199. Del Vescovo V, Meier T, Inga A, Denti MA, Borlak J. A cross-platform comparison of affymetrix and agilent microarrays reveals discordant miRNA expression in lung tumors of c-Raf transgenic mice. PLoS ONE. 2013;8(11):e78870. doi:10.1371/journal.pone.0078870.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  200. Luo H, Zhang H, Zhang Z, Zhang X, Ning B, Guo J, et al. Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res. 2009;28:82. doi:10.1186/1756-9966-28-82.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  201. Yang O, Huang J, Lin S. Regulatory effects of miRNA on gastric cancer cells. Oncol Lett. 2014;8(2):651–6. doi:10.3892/ol.2014.2232.

    CAS  PubMed Central  PubMed  Google Scholar 

  202. Guo LH, Li H, Wang F, Yu J, He JS. The tumor suppressor roles of miR-433 and miR-127 in gastric cancer. Int J Mol Sci. 2013;14(7):14171–84. doi:10.3390/ijms140714171.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  203. Yan Z, Shah PK, Amin SB, Samur MK, Huang N, Wang X, et al. Integrative analysis of gene and miRNA expression profiles with transcription factor-miRNA feed-forward loops identifies regulators in human cancers. Nucleic Acids Res. 2012;40(17):e135. doi:10.1093/nar/gks395.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  204. Lee YJ, Kim V, Muth DC, Witwer KW. Validated microRNA target databases: an evaluation. Drug Dev Res. 2015;76(7):389–96. doi:10.1002/ddr.21278.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  205. Dweep H, Gretz N. miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods. 2015;12(8):697. doi:10.1038/nmeth.3485.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81372856) and Taishan Scholars Program of Shandong Province (No. ts201511096). We thank Dr. Hsin-Sheng Yang (Graduate Center for Toxicology, University of Kentucky) and Dr. Tiantian Liu (Department of Pathology, School of Medicine, Shandong University) for their critical reading and suggestions for the manuscript.

Author information

Authors and Affiliations

  1. Department of Pathology, School of Medicine, Shandong University, **an, 250012, People’s Republic of China

    Ya-Wen Wang, Xu Chen & Peng Gao

  2. Department of Breast Surgery, Qilu Hospital of Shandong University, **an, 250012, People’s Republic of China

    Ya-Wen Wang & Rong Ma

Authors
  1. Ya-Wen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peng Gao.

Ethics declarations

Conflicts of interest

None

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource Figure S1

Relationship between CREB1 and miR-27b in gastric cancer, and potential regulation of CREB1 on miR-27b. (a) The expression of CREB1 and miR-27b were detected respectively by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in gastric cancer tissues (for more detail, see our previous paper: Wang et al. Oncotarget. 2015). Spearman’s correlation analysis showed that CREB1 was positively correlated with miR-27b in gastric cancer tissues (r = 0.3563, P = 0.0007). (b–c) miRStart (http://mirstart.mbc.nctu.edu.tw/home.php) was utilized to get the putative transcription start sites and promoter sequences of miR-27b. Then the potential biding sites for CREB1 were predicted by RegRNA2.0 (http://regrna2.mbc.nctu.edu.tw/detection.html) and PROMO database (http://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi?dirDB = TF_8.3). The analysis revealed the presence of several CREB1-binding sites in the putative promoter of miR-27b (PDF 83 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, YW., Chen, X., Ma, R. et al. Understanding the CREB1-miRNA feedback loop in human malignancies. Tumor Biol. 37, 8487–8502 (2016). https://doi.org/10.1007/s13277-016-5050-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5050-x

Keywords

Search

Navigation