Abstract
Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in the development of several human cancers. MIR31HG, an lncRNA located in 9p21.3 and 2166 bp in length, has been found to be upregulated in breast cancer and contributes to cell proliferation and invasion. However, the expression pattern and biological function of MIR31HG in gastric cancer are still not well documented. In this study, we found that MIR31HG expression is decreased in gastric cancer tissues and associated with larger tumor size and advanced pathological stage. Patients with lower MIR31HG expression had a relatively poor prognosis. Furthermore, ectopic over-expression of MIR31HG could inhibit gastric cancer (GC) cell proliferation both in vitro and in vivo, while knockdown of MIR31HG by small interfering RNA (siRNA) promoted cell proliferation in GC cells partly via regulating E2F1 and p21 expression. Our findings present that decreased MIR31HG is involved in GC development and could be identified as a poor prognostic biomarker in GC patients.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4644-z/MediaObjects/13277_2015_4644_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4644-z/MediaObjects/13277_2015_4644_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4644-z/MediaObjects/13277_2015_4644_Fig3_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4644-z/MediaObjects/13277_2015_4644_Fig4_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-4644-z/MediaObjects/13277_2015_4644_Fig5_HTML.gif)
Similar content being viewed by others
References
DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin. 2011;61(6):409–18. doi:10.3322/caac.20134.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. doi:10.3322/caac.21208.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30. doi:10.3322/caac.21166.
Jung KW, Won YJ, Kong HJ, Oh CM, Lee DH, Lee JS. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2011. Cancer Res Treat. 2014;46(2):109–23. doi:10.4143/crt.2014.46.2.109.
Ling H, Vincent K, Pichler M, Fodde R, Berindan-Neagoe I, Slack FJ, et al. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene. 2015. doi:10.1038/onc.2014.456.
Yarmishyn AA, Kurochkin IV. Long noncoding RNAs: a potential novel class of cancer biomarkers. Front Genet. 2015;6:145. doi:10.3389/fgene.2015.00145.
Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for the ENCODE Project. Genome Res. 2012;22(9):1760–74. doi:10.1101/gr.135350.111.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89. doi:10.1101/gr.132159.111.
Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26–46. doi:10.1016/j.cell.2013.06.020.
Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477(7364):295–300. doi:10.1038/nature10398.
Grote P, Wittler L, Hendrix D, Koch F, Wahrisch S, Beisaw A, et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell. 2013;24(2):206–14. doi:10.1016/j.devcel.2012.12.012.
Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011;43(7):621–9. doi:10.1038/ng.848.
Sun M, Liu XH, Lu KH, Nie FQ, **a R, Kong R, et al. EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition. Cell Death Dis. 2014;5:e1298. doi:10.1038/cddis.2014.256.
Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43(6):904–14. doi:10.1016/j.molcel.2011.08.018.
Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66. doi:10.1146/annurev-biochem-051410-092902.
Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8. doi:10.1016/j.cell.2011.07.014.
Shi X, Sun M, Wu Y, Yao Y, Liu H, Wu G, et al. Post-transcriptional regulation of long noncoding RNAs in cancer. Tumour Biol. 2015;36(2):503–13. doi:10.1007/s13277-015-3106-y.
Shi Y, Lu J, Zhou J, Tan X, He Y, Ding J, et al. Long non-coding RNA Loc554202 regulates proliferation and migration in breast cancer cells. Biochem Biophys Res Commun. 2014;446(2):448–53. doi:10.1016/j.bbrc.2014.02.144.
Montes M, Nielsen MM, Maglieri G, Jacobsen A, Hojfeldt J, Agrawal-Singh S, et al. The lncRNA MIR31HG regulates p16(INK4A) expression to modulate senescence. Nat Commun. 2015;6:6967. doi:10.1038/ncomms7967.
Gan L, Xu M, Zhang Y, Zhang X, Guo W. Focusing on long noncoding RNA dysregulation in gastric cancer. Tumour Biol. 2015;36(1):129–41. doi:10.1007/s13277-014-2894-9.
Fatima R, Akhade VS, Pal D, Rao SM. Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets. Mol Cell Ther. 2015;3:5. doi:10.1186/s40591-015-0042-6.
Khandelwal A, Bacolla A, Vasquez KM, Jain A. Long non-coding RNA: a new paradigm for lung cancer. Mol Carcinog. 2015. doi:10.1002/mc.22362.
Yan X, Hu Z, Feng Y, Hu X, Yuan J, Zhao SD, et al. Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell. 2015;28(4):529–40. doi:10.1016/j.ccell.2015.09.006.
Thorenoor N, Faltejskova-Vychytilova P, Hombach S, Mlcochova J, Kretz M, Svoboda M et al. Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer. Oncotarget. 2015. doi: 10.18632/oncotarget.5807.
Hu Y, Wang J, Qian J, Kong X, Tang J, Wang Y, et al. Long noncoding RNA GAPLINC regulates CD44-dependent cell invasiveness and associates with poor prognosis of gastric cancer. Cancer Res. 2014;74(23):6890–902. doi:10.1158/0008-5472.CAN-14-0686.
Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer. 2014;13:92. doi:10.1186/1476-4598-13-92.
**e M, Sun M, Zhu YN, **a R, Liu YW, Ding J et al. Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression. Oncotarget. 2015;6(32):33587–601. doi: 10.18632/oncotarget.5599.
Ding J, Lu B, Wang J, Shi Y, Lian Y, Zhu Y, et al. Long non-coding RNA Loc554202 induces apoptosis in colorectal cancer cells via the caspase cleavage cascades. J Exp Clin Cancer Res. 2015;34:100. doi:10.1186/s13046-015-0217-7.
Yang H, Liu P, Zhang J, Peng X, Lu Z, Yu S, et al. Long noncoding RNA MIR31HG exhibits oncogenic property in pancreatic ductal adenocarcinoma and is negatively regulated by miR-193b. Oncogene. 2015. doi:10.1038/onc.2015.430.
Huang CL, Liu D, Nakano J, Yokomise H, Ueno M, Kadota K, et al. E2F1 overexpression correlates with thymidylate synthase and survivin gene expressions and tumor proliferation in non small-cell lung cancer. Clin Cancer Res. 2007;13(23):6938–46. doi:10.1158/1078-0432.CCR-07-1539.
Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging. Cell. 2006;127(2):265–75. doi:10.1016/j.cell.2006.10.003.
Acknowledgments
This work was supported by the National Scientific Foundation of China (No. 81301824) and National Scientific Foundation of Jiangsu Provincial of China (BK20141437).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the Research Ethics Committee of Nan**g Medical University, China. Informed consents were obtained from all patients.
Conflicts of interest
None
Additional information
Feng-qi Nie, Shijie Ma, and Min **e contributed equally to this work and should be regarded as joint first authors.
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
Primers and siRNA sequence. (XLS 24 kb)
Rights and permissions
About this article
Cite this article
Nie, Fq., Ma, S., **e, M. et al. Decreased long noncoding RNA MIR31HG is correlated with poor prognosis and contributes to cell proliferation in gastric cancer. Tumor Biol. 37, 7693–7701 (2016). https://doi.org/10.1007/s13277-015-4644-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4644-z