Skip to main content

Advertisement

SpringerLink
Log in

Differentially expressed miR-20, miR-21, miR-100, miR-125a and miR-146a as a potential biomarker for prostate cancer

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Prostate cancer is the leading cause of death among men worldwide. Deregulation of microRNAs has been reported in many cancers. Expression of microRNAs miR-20a-5p, miR-21-5p, miR-100-5p, miR-125a-5p and miR-146a-5p in tissue blocks of histologically confirmed prostate cancer patients compared with BPH patients, to identify potential microRNA biomarker for prostate cancer. MicroRNA was isolated and expression was quantified by qRT-PCR using Taqman Advanced microRNA assay kits. The interactions between the microRNA:target mRNA were predicted by using bioinformatics tools such as miRwalk and miRTargetlink. The experimentally validated targets were analysed using gprofiler to identify their molecular function, biological process and related pathways. The expression analysis revealed that miR-21 and miR-100 were significantly down-regulated whereas miR-125a was up-regulated in prostate cancer patients. Comparative analysis of the expression levels with tumor grading reveal that miR-100 was significantly down-regulated (p < 0.05) in high grade tumor, indicating that miR-100 associated with prostate cancer. ROC analysis revealed that combined analysis of down-regulated miRNAs (miR-21 and miR-100) shown AUC of 0.72 (95% CI 0.65–0.79). The combined analysis of all five miRNAs showed AUC of 0.87 (95% CI 0.81–0.92). The targets prediction analysis revealed several validated targets including BCL2, ROCK1, EGFR, PTEN, MTOR, NAIF1 and VEGFA. Our results provide evidence that combined analysis of all the five miRNAs as a panel can significantly improve the prediction level of the presence of prostate cancer and may be used as a potential diagnostic biomarker.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

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. Rawla P (2019) Epidemiology of prostate cancer. World journal of oncology 10(2):63. https://doi.org/10.14740/wjon1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jain S, Saxena S, Kumar A (2014) Epidemiology of prostate cancer in India. Meta Gene 2:596–605. https://doi.org/10.1016/j.mgene.2014.07.007

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cary KC, Cooperberg MR (2013) Biomarkers in prostate cancer surveillance and screening: past, present, and future. Ther Adv Urol 5(6):318–329. https://doi.org/10.1177/1756287213495915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Adhyam M, Gupta AK (2012) A review on the clinical utility of PSA in cancer prostate. Indian J Surg Oncol 3(2):120–129. https://doi.org/10.1007/s13193-012-0142-6

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ayub SG, Kaul D, Ayub T (2015) Microdissecting the role of microRNAs in the pathogenesis of prostate cancer. Cancer Genet 208(6):289–302. https://doi.org/10.1016/j.cancergen.2015.02.010

    Article  CAS  PubMed  Google Scholar 

  6. Ewquela-Kerscher A, Slack FJ (2006) Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269. https://doi.org/10.1038/nrc1840

    Article  CAS  Google Scholar 

  7. Kasinski AL, Slack FJ (2011) MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer 11(12):849–864. https://doi.org/10.1038/nrc3166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stahlhut C, Slack FJ (2013) MicroRNAs and the cancer phenotype: profiling, signatures and clinical implications. Genome Med 5(12):111. https://doi.org/10.1186/gm516

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wach S, Nolte E, Szczyrba J et al (2012) MicroRNA profiles of prostate carcinoma detected by multiplatform microRNA screening. Int J Cancer 130(3):611–621. https://doi.org/10.1002/ijc.26064

    Article  CAS  PubMed  Google Scholar 

  10. Carlsson J, Davidsson S, Helenius G et al (2011) A miRNA expression signature that separates between normal and malignant prostate tissues. Cancer Cell Int 11(1):14. https://doi.org/10.1186/1475-2867-11-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhong J, Huang R, Su Z et al (2017) Downregulation of miR-199a-5p promotes prostate adeno-carcinoma progression through loss of its inhibition of HIF-1α. Oncotarget 8(48):83523. https://doi.org/10.18632/oncotarget.18315

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jia HY, Wang YX, Yan WT et al (2012) MicroRNA-125b functions as a tumor suppressor in hepatocellular carcinoma cells. Int J Mol Sci. https://doi.org/10.3390/ijms13078762

    Article  PubMed  PubMed Central  Google Scholar 

  13. Damodaran M, Paul SF, Venkatesan V (2020) Genetic polymorphisms in miR-146a, miR-196a2 and miR-125a genes and its association in prostate cancer. Pathol Oncol Res. https://doi.org/10.1007/s12253-018-0412-x

    Article  PubMed  Google Scholar 

  14. Epstein JI, Zelefsky MJ, Sjoberg DD et al (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3):428–435. https://doi.org/10.1016/j.eururo.2015.06.046

    Article  PubMed  Google Scholar 

  15. Kiener M, Chen L, Krebs M et al (2019) miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo. BMC Cancer. https://doi.org/10.1186/s12885-019-5819-6

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Hamberg M, Backes C, Fehlmann T et al (2016) MiRTargetLink—miRNAs, genes and interaction networks. Int J Mol Sci 4:564. https://doi.org/10.3390/ijms17040564

    Article  CAS  Google Scholar 

  18. Jüri R, Meelis K, Hedi P et al (2007) g: Profiler-a web-based toolset for functional profiling of gene lists from large-scale expriments. Nuc Aci Res 35:w193-200. https://doi.org/10.1093/nar/gkm226

    Article  Google Scholar 

  19. https://www.socscistatistics.com/tests/studentttest/default.aspxs

  20. Ding HY, Qian WQ, Xu J (2016) MicroRNA-146b acts as a potential tumor suppressor in human prostate cancer. J Balk Union Oncol 21:434–443

    Google Scholar 

  21. Porkka KP, Pfeiffer MJ, Waltering KK et al (2007) MicroRNA expression profiling in prostate cancer. Can Res 67(13):6130–6135. https://doi.org/10.1158/0008-5472

    Article  Google Scholar 

  22. Filella X, Foj L (2017) miRNAs as novel biomarkers in the management of prostate cancer. Clin Chem Lab Med 55(5):715–36. https://doi.org/10.1515/cclm-2015-1073

    Article  CAS  PubMed  Google Scholar 

  23. Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302(1):1–12. https://doi.org/10.1016/j.ydbio.2006.08.028

    Article  CAS  PubMed  Google Scholar 

  24. Henson BJ, Bhattacharjee S, O’Dee DM et al (2009) Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. Genes Chromosom Cancer 48(7):569–582. https://doi.org/10.1002/gcc.20666

    Article  CAS  PubMed  Google Scholar 

  25. Volinia S, Calin GA, Liu CG, Ambs S et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103(7):2257–2261

    Article  CAS  Google Scholar 

  26. Li C, Gao Y, Zhang K et al (2015) Multiple roles of microRNA-100 in human cancer and its therapeutic potential. Cell Physiol Biochem 37(6):2143–2159. https://doi.org/10.1159/000438572

    Article  CAS  PubMed  Google Scholar 

  27. Leite KR, Morais DR, Reis ST, Viana N et al (2013) MicroRNA 100: a context dependent miRNA in prostate cancer. Clinics 68(6):797–802. https://doi.org/10.6061/clinics/2013(06)12

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fu Y, Cao F (2015) MicroRNA-125a-5p regulates cancer cell proliferation and migration through NAIF1 in prostate carcinoma. Onco Targets Ther 8:3827. https://doi.org/10.2147/OTT.S92314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was financially supported by Department of Biotechnology, Government of India 6242-P58/RGCB/PMD/DBT/VVSL/2015.

Funding

This work was financially supported by Department of Biotechnology, Government of India 6242-P58/RGCB/PMD/DBT/VVSL/2015.

Author information

Authors and Affiliations

  1. Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, 600116, India

    Mohan Damodaran & Vettriselvi Venkatesan

  2. Central Research Facility, Sri Ramachandra Institute of Higher Education and Research, Chennai, India

    Mohanapriya Chinambedu Dandapani

  3. Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India

    SimonDuraiRaj &  SandhyaSundaram

  4. Department of Urology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India

    S. VenkatRamanan

  5. Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, India

    Ilangovan Ramachandran

Authors
  1. Mohan Damodaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohanapriya Chinambedu Dandapani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. SimonDuraiRaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. SandhyaSundaram
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. VenkatRamanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ilangovan Ramachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vettriselvi Venkatesan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

I would like to acknowledge all the authors who have contributed significantly to this paper; MD, has given the substantial contribution in data collection, analysis, interpretation of the data and drafting the manuscript. MCD, SDR and SS helped and contributed samples for the study, SVR and RI provided external supervision for the research activity. Revision and final approval of the version to be published and the primary responsibility for communication with the journal during manuscript submission was done by VV (Corresponding author).

Corresponding author

Correspondence to Vettriselvi Venkatesan.

Ethics declarations

Conflict of interest

The authors did not have any conflict of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Damodaran, M., Chinambedu Dandapani, M., SimonDuraiRaj et al. Differentially expressed miR-20, miR-21, miR-100, miR-125a and miR-146a as a potential biomarker for prostate cancer. Mol Biol Rep 48, 3349–3356 (2021). https://doi.org/10.1007/s11033-021-06384-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06384-z

Keywords

Search

Navigation