SpringerLink
Log in

Expression profiles of miR-196, miR-132, miR-146a, and miR-134 in human colorectal cancer tissues in accordance with their clinical significance

Comparison regarding KRAS mutation

  • original article
  • Published:
Wiener klinische Wochenschrift Aims and scope Submit manuscript

Summary

Background

Colorectal cancer (CRC) is among the most widespread malignancies in the world. MicroRNA (miRNA) has been identified as an important modulator of the biological processes of the cells. This group of noncoding RNAs also has a pivotal function in the growth and development of human cancers, including CRC. Among these miRNAs, miR-196, miR-132, miR-146a, and miR-134 have fundamental impacts on the regulation of cancers. The current study aimed to investigate the involvement of these miRNAs in CRC patients.

Methods

In this study, 50 pairs of tumor and tumor margin samples of CRC patients were investigated to assess the expression levels of miR-196, miR-132, miR-146a, and miR-134 in this cancer. For this purpose, firstly, quantitative real-time PCR (qRT-PCR) was applied. Also, KRAS mutation and clinicopathological characteristics of the CRC patients were analyzed in the study groups.

Results

The findings demonstrated the overexpression of miR-196 (P-value = 0.0045) and miR-146a (P-value = 0.0033) in tumor tissues compared to controls. Conversely, the expression levels of miR-132 (P-value = 0.00032) and miR-134 (P-value < 0.0001) were downregulated in tumor tissues. Also, miR-146a was the only miRNA with significant expression change in the case of the KRAS gene mutation. Interestingly, the expression ratio of these miRNAs was significantly associated with some of the clinicopathological features of the patients, such as lymph node and distant metastases.

Conclusion

Our data demonstrated that these miRNAs appear to be promising novel biomarkers for early diagnosis of CRC and may pave the way for the future establishment of novel therapeutic options for CRC.

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 (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. Ca A Cancer J Clin. 2015;65:87–108.

    Google Scholar 

  2. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144:1941–53.

    CAS  PubMed  Google Scholar 

  3. Shirafkan N, Mansoori B, Mohammadi A, Shomali N, Ghasbi M, Baradaran B. MicroRNAs as novel biomarkers for colorectal cancer: new outlooks. Biomed Pharmacother. 2018;97:1319–30.

    CAS  PubMed  Google Scholar 

  4. Esmailzadeh S, Mansoori B, Mohammadi A, Shanehbandi D, Baradaran B. siRNA-mediated silencing of HMGA2 induces apoptosis and cell cycle arrest in human colorectal carcinoma. J Gastrointest Cancer. 2017;48:156–63.

    CAS  PubMed  Google Scholar 

  5. Corté H, Manceau G, Blons H, Laurent-Puig P. MicroRNA and colorectal cancer. Dig Liver Dis. 2012;44:195–200.

    PubMed  Google Scholar 

  6. Gonzalez-Pons M, Cruz-Correa M. Colorectal cancer biomarkers: Where are we now? Biomed Res Int. 2015; https://doi.org/10.1155/2015/149014.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010;1803:1231–43.

    CAS  PubMed  Google Scholar 

  8. Ghasabi M, Mansoori B, Mohammadi A, Duijf PH, Shomali N, Shirafkan N, et al. MicroRNAs in cancer drug resistance: basic evidence and clinical applications. J Cell Physiol. 2019;234:2152–68.

    CAS  PubMed  Google Scholar 

  9. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.

    CAS  PubMed  Google Scholar 

  10. Mohammadi A, Mansoori B, Baradaran B. The role of microRNAs in colorectal cancer. Biomed Pharmacother. 2016;84:705–13.

    CAS  PubMed  Google Scholar 

  11. Karami H, Baradaran B, Esfahani A, Estiar MA, Naghavi-Behzad M, Sakhinia M, et al. siRNA-mediated silencing of survivin inhibits proliferation and enhances etoposide chemosensitivity in acute myeloid leukemia cells. Asian Pac J Cancer Prev. 2013;14:7719–24.

    PubMed  Google Scholar 

  12. Suzuki H, Takatsuka S, Akashi H, Yamamoto E, Nojima M, Maruyama R, et al. Genome-wide profiling of chromatin signatures reveals epigenetic regulation of microRNA genes in colorectal cancer. Cancer Res. 2011;71:5646–58.

    CAS  PubMed  Google Scholar 

  13. Wang YX, Zhang XY, Zhang BF, Yang CQ, Chen XM, Gao HJ. Initial study of microRNA expression profiles of colonic cancer without lymph node metastasis. J Dig Dis. 2010;11:50–4.

    PubMed  Google Scholar 

  14. Bin Zheng Y, Luo HP, Shi Q, Hao ZN, Ding Y, Wang QS, et al. miR-132 inhibits colorectal cancer invasion and metastasis via directly targeting ZEB2. World J Gastroenterol. 2014;20:6515–22.

    PubMed  PubMed Central  Google Scholar 

  15. Formosa A, Lena AM, Markert EK, Cortelli S, Miano R, Mauriello A, et al. DNA methylation silences miR-132 in prostate cancer. Oncogene. 2013;32:127–34.

    CAS  PubMed  Google Scholar 

  16. Zhang S, Hao J, **e F, Hu X, Liu C, Tong J, et al. Downregulation of miR-132 by promoter methylation contributes to pancreatic cancer development. Carcinogenesis. 2011;32:1183–9.

    CAS  PubMed  Google Scholar 

  17. Qin J, Ke J, Xu J, Wang F, Zhou Y, Jiang Y, et al. Downregulation of microRNA -132 by DNA hypermethylation is associated with cell invasion in colorectal cancer. Onco Targets Ther. 2015;8:3639–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chae YS, Kim JG, Lee SJ, Kang BW, Lee YJ, Park JYJS, et al. A miR-146a polymorphism (rs2910164) predicts risk of and survival from colorectal cancer. Anticancer Res. 2013;33:3233–40.

    CAS  PubMed  Google Scholar 

  19. Philippidou D, Schmitt M, Moser D, Margue C, Nazarov PV, Muller A, et al. Signatures of MicroRNAs and selected MicroRNA target genes in human melanoma. Cancer Res. 2010;70:4163–73.

    CAS  PubMed  Google Scholar 

  20. Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. Plos One. 2008;3(7):e2557.

    PubMed  PubMed Central  Google Scholar 

  21. Sun M, Fang S, Li W, Li C, Wang L, Wang F, et al. Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma. Cancer Biomark. 2015;15:33–40.

    CAS  PubMed  Google Scholar 

  22. Ye Q, Su L, Chen D, Zheng W, Liu Y. Astragaloside IV induced MIR-134 expression reduces EMT and increases chemotherapeutic sensitivity by suppressing CREB1 signaling in colorectal cancer cell line SW-480. Cell Physiol Biochem. 2017;43:1617–26.

    CAS  PubMed  Google Scholar 

  23. Aghaee F, Pirayesh Islamian J, Baradaran B. Enhanced radiosensitivity and chemosensitivity of breast cancer cells by 2‑deoxy-D-glucose in combination therapy. J Breast Cancer. 2012;15:141.

    PubMed  PubMed Central  Google Scholar 

  24. Hajiasgharzadeh K, Tavangar SM, Javan M, Dehpour AR, Mani AR. Does hepatic vagus nerve modulate the progression of biliary fibrosis in rats? Auton Neurosci. 2014;185:67–75.

    CAS  PubMed  Google Scholar 

  25. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25:402–8.

    CAS  PubMed  Google Scholar 

  26. Daryabari SS, Safaralizadeh R, Hosseinpourfeizi M, Moaddab Y, Shokouhi B. Overexpression of SSH1 in gastric adenocarcinoma and its correlation with clinicopathological features. J Gastrointest Oncol. 2018;9:728–33.

    PubMed  PubMed Central  Google Scholar 

  27. Madhavan D, Cuk K, Burwinkel B, Yang R. Cancer diagnosis and prognosis decoded by blood-based circulating micro RNA signatures. Front Genet. 2013;4:116.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Thome AD, Harms AS, Volpicelli-Daley LA, Standaert DG. MicroRNA-155 regulates alpha-synuclein-induced inflammatory responses in models of Parkinson disease. J Neurosci. 2016;36:2383–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML, Tamehiro N, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328(5985):1570–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ahmed FE, Ahmed NC, Vos PW, Bonnerup C, Atkins JN, Casey M, et al. Diagnostic MicroRNA markers to screen for sporadic human colon cancer in stool: I. Proof of principle. Cancer Genomics Proteomics. 2013;10:93–113.

    CAS  PubMed  Google Scholar 

  31. Iannone A, Losurdo G, Pricci M, Girardi B, Massaro A, Principi M, et al. Stool investigations for colorectal cancer screening: from occult blood test to DNA analysis. J Gastrointest Cancer. 2016;47:143–51.

    CAS  PubMed  Google Scholar 

  32. Schimanski CC, Frerichs K, Rahman F, Berger M, Lang H, Galle PR, et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterol. 2009;15:2089–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ge J, Chen Z, Li R, Lu T, **ao G. Upregulation of microRNA-196a and microRNA-196b cooperatively correlate with aggressive progression and unfavorable prognosis in patients with colorectal cancer. Cancer Cell Int. 2014;14:128.

    PubMed  PubMed Central  Google Scholar 

  34. Chen CJ, Zhang Y, Zhang L, Weakley SM, Yao Q. MicroRNA-196: critical roles and clinical applications in development and cancer. J Cell Mol Med. 2011;15:14–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Shen S, Pan J, Lu X, Chi P. Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression. Oncol Lett. 2016;12:4041–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Geng F, Wu JL, Lu GF, Liang ZP, Duan ZL, Gu X. MicroRNA-132 targets PEA-15 and suppresses the progression of astrocytoma in vitro. J Neurooncol. 2016;129:211–20.

    CAS  PubMed  Google Scholar 

  37. Zhang B, Lu L, Zhang X, Ye W, Wu J, ** Q, et al. Hsa-miR-132 regulates apoptosis in non-small cell lung cancer independent of acetylcholinesterase. J Mol Neurosci. 2014;53:335–44.

    CAS  PubMed  Google Scholar 

  38. Alzahrani AM, Hanieh H, Ibrahim H‑IM, Mohafez O, Shehata T, Bani Ismail M, et al. Enhancing miR-132 expression by aryl hydrocarbon receptor attenuates tumorigenesis associated with chronic colitis. Int Immunopharmacol. 2017;52:342–51.

    CAS  PubMed  Google Scholar 

  39. Xu G, Zhu H, Zhang M, Xu J. Histone deacetylase 3 is associated with gastric cancer cell growth via the miR-454-mediated targeting of CHD5. Int J Mol Med. 2018;41:155–63.

    CAS  PubMed  Google Scholar 

  40. Wu J, He D, Yue B, Zhang C, Fang X, Chen H. miR-101‑1 expression pattern in Qinchuan cattle and its role in the regulation of cell differentiation. Gene. 2017;636:64–9.

    CAS  PubMed  Google Scholar 

  41. Chen G, Umelo IA, Lv S, Teugels E, Fostier K, Kronenberger P, et al. miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One. 2013;8:e60317.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Yao Q, Cao Z, Tu C, Zhao Y, Liu H, Zhang S. MicroRNA-146a acts as a metastasis suppressor in gastric cancer by targeting WASF2. Cancer Lett. 2013;335:219–24.

    CAS  PubMed  Google Scholar 

  43. Pizzini S, Bisognin A, Mandruzzato S, Biasiolo M, Facciolli A, Perilli L, et al. Impact of microRNAs on regulatory networks and pathways in human colorectal carcinogenesis and development of metastasis. BMC Genomics. 2013;14:589.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Mao Y, Li Y, **g F, Cai S, Zhang Z, Li Q, et al. Association of a genetic variant in microRNA-146a with risk of colorectal cancer: a population-based case-control study. Tumor Biol. 2014;35:6961–7.

    CAS  Google Scholar 

  45. Wang C, Guan S, Liu F, Chen X, Han L, Wang D, et al. Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma. Br J Cancer. 2016;114:290–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Niu CS, Yang Y, Cheng CD. MiR-134 regulates the proliferation and invasion of glioblastoma cells by reducing Nanog expression. Int J Oncol. 2013;42:1533–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Leivonen SK, Sahlberg KK, Mäkelä R, Due EU, Kallioniemi O, Børresen-Dale AL, et al. High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Mol Oncol. 2014;8:93–104.

    CAS  PubMed  Google Scholar 

  48. Liu CJ, Shen WG, Peng SY, Cheng HW, Kao SY, Lin SC, et al. MiR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene. Int J Cancer. 2014;134:811–21.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the Immunology Research Center, Tabriz University of Medical Sciences for providing facilities to carry out this work.

Author information

Authors and Affiliations

  1. Phase I-Early Clinical Trials Unit, Department of Oncology, Antwerp University Hospital (UZA) and Center for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium

    Mahafarin Maralani & Marc Peeters

  2. Department of Medical Oncology, Azienda hospital polyclinic of “Paolo Giaccone”, University of “Degli studi di palermo”, Palermo, Italy

    Mahafarin Maralani

  3. Immunology Research Center, Tabriz University of Medical Sciences, 5166614766, Tabriz, Iran

    Dariush Shanehbandi, Milad Asadi, Khalil Hajiasgharzadeh & Behzad Baradaran

  4. Department of Thoracic Surgery, Tabriz University of Medical Sciences, Tabriz, Iran

    Shahriar Hashemzadeh

  5. Tabriz Health Services Management Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran

    Hossein Mashhadi Abdolahi

Authors
  1. Mahafarin Maralani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dariush Shanehbandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Milad Asadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahriar Hashemzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Khalil Hajiasgharzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hossein Mashhadi Abdolahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Behzad Baradaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marc Peeters
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MM, DS, MA, SH, and HMA performed the experiments. BB provided biological materials and reagents. MM and KH wrote the initial draft of the article. MM, DS, MA, and BB performed data analysis. BB and MP reviewed and edited the article. BB supervised the study.

Corresponding author

Correspondence to Behzad Baradaran.

Ethics declarations

Conflict of interest

M. Maralani, D. Shanehbandi, M. Asadi, S. Hashemzadeh, K. Hajiasgharzadeh, H. Mashhadi Abdolahi, B. Baradaran and M. Peeters declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee (Ethics committee of Tabriz University of Medical Sciences, Tabriz, Iran) and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maralani, M., Shanehbandi, D., Asadi, M. et al. Expression profiles of miR-196, miR-132, miR-146a, and miR-134 in human colorectal cancer tissues in accordance with their clinical significance. Wien Klin Wochenschr 133, 1162–1170 (2021). https://doi.org/10.1007/s00508-021-01933-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-021-01933-9

Keywords

Search

Navigation