Mir-15A Reconstitution in Prostate Cancer Cell Line Suppresses Cancer Progression Through Down Regulation of MYB and Androgen Receptor Upregulation

Open access


Prostate cancer is one of the most common malignancies and the second leading cause of death from cancer in men. MicroRNAs are noncoding RNAs that have a role of post-transcriptional regulators. In this study we investigated how the tumour suppressor miR-15a modulates main transcription factors like cMYB and AR in androgen sensitive prostate cancer cell line LNCaP. The miR-15a inhibitor, mimic, and their negative controls were transfected into LNCaP cells. Real-time PCR analysis was performed in order to estimate the transcript levels of cMYB and AR. Flow cytometry analysis was performed to measure the protein levels of cMYB and AR. A Cell migration assay was done for cells transfected with miR-15a inhibitor and mimic. We found that cMYB is down-regulated and AR is up-regulated by miR-15a on the transcriptional and protein levels. By reconstituting miR-15a, we found that its down regulation in prostate cancer contributes to cMYB-induced cancer progression and reduced androgen receptivity. The ability of miR-15a to suppress cancer cell viability and migration is a very important phenomenon for understanding cancer heterogeneity in regard to adapted therapeutic approach development.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Aqeilan R. I. Calin G. A. Croce C. M. miR-15a and miR-16-1 in cancer: discovery function and future perspectives. - Cell Death Differ. 17 2010 215-220.

  • 2. Calin G. A. C. D. Dumitru M. Shimizu et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. - Proc Natl Acad Sci USA 26 200299(24)15524-9.

  • 3. Cimmino A. G. A. Calin M. Fabbri et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. - Proc. Natl. Acad. Sci. USA 27 2005 102(39) 13944-9.

  • 4. Heinlein C. A. et C. Chang. Androgen receptor in prostate cancer. - Endocr. Rev. 25 2004 N 2 276-308.

  • 5. Jun-jie YU and XIA Shu-jie. Novel role of microRNAs in prostate cancer. - Chin. Med. J. 126 2013; N15 2960-4.

  • 6. Kalkbrenner F. S. Guehmann et K. Moelling. Transcriptional activation by human c-myb and v-myb genes. - Oncogene 5 1990 N 5 657-661.

  • 7. Lagos-Quintana M. R. Rauhut A. Yalcin et al. Identification of tissue-specific MicroRNAs from mouse. - Curr. Biol. 12 2002 N9 735-739.

  • 8. Lin J. Q. Cao J. Zhang et al. MicroRNA expression patterns in indeterminate inflammatory bowel disease. - Mod. Pathol. 26 2013 N1148-154.

  • 9. Musumeci M. V. Coppola A. Addario et al. Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. - Oncogene 30 2011 4231-4242.

  • 10. Narayanan R. J. Jiang Y. Gusevetal. Micrornasaremediators of androgen action in prostate and muscle. - PLoS ONE 5 2010 N10 Article ID e13637.

  • 11. Nicolaides N. C. R. Gualdi C. Casadevall et al. Positive autoregulation of c-myb expression via Myb binding sites in the 5 flanking region of the human c-myb gene. - Mol. Cell. Biol. 11 1991 N12 6166-6176.

  • 12. Oudai H. A. Ahmad S. Sethi et F. H Sarkar. Recent updates on the role of microRNAs in prostate cancer. - J. Hematol. Oncol. 5:9 2012 doi:10.1186/1756-8722-5-9.

  • 13. Shen M. M. et C. Abate-Shen. Molecular genetics of prostate cancer: New prospects for old challenges. - Genes and Development 24 2010 N18 1967-2000.

  • 14. Sullivan R. S. Schneider J. Leong et T. Fehniger. Mir-15/16 antagonizes c-Myb to control natural killer cell maturation (LYM7P.714). - J. Immunol. 192 2014 (1 Supplement) 193.2

  • 15. Zhao H. A. Kalota S. Jin et A. M. Gewirtz. The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory feedback loop in human hematopoietic cells. - Blood. 113 2009; 505-516.

Journal information
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 246 84 4
PDF Downloads 104 39 5