MicroRNAs in Prostate Cancer: A Possible Role as Novel Biomarkers and Therapeutic Targets?
Eradication of advanced prostate cancer still represents an unsolved clinical problem, making the development of alternative treatment approaches highly desirable. Understanding the molecular alterations that distinguish the non-progressive from progressive disease will allow the identification of novel biomarkers for improved staging and prognostication, and will also provide mechanistic information to facilitate treatment selection and design of novel therapeutic approaches. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression. Recent findings indicate that miRNAs are deregulated in human tumors, suggesting a potential role for these molecules in the pathogenesis of cancer. Thus far, only a limited number of studies have investigated miRNA expression in prostate cancer. Results indicate that miRNA expression profiles may distinguish carcinoma from non-neoplastic specimens and further classify tumors according to androgen dependence. In addition, a prognostic significance has been attributed to specific miRNAs as predictors of clinical recurrence following radical prostatectomy. These findings, together with the documented possibility to detect cancer-related miRNAs in blood and core biopsies, open a window on the possibility to utilize them as novel biomarkers. For a handful of miRNAs, functional investigation has also been pursued in prostate cancer experimental models to establish the rationale for the development of miRNA-based therapies. However, a better understanding of the role exerted by specific miRNAs in the onset and progression of prostate cancer is needed, as is a precise definition of their targets relevant to the disease, before translating these molecules into the clinical setting.
KeywordsBenign Prostatic Hyperplasia Radical Prostatectomy miRNA Expression Gleason Score miRNA Expression Profile
- Dong Q, Meng P, Wang T, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5:e10147.Google Scholar
- Folini M, Gandellini P, Longoni N, et al. MiR-21: an oncomir on strike in prostate cancer. Mol Cancer. 2010;9:12.Google Scholar
- Fontana L, Fiori ME, Albini S, et al. Antagomir-17-5pabolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One. 2008;3:e2236.Google Scholar
- Fujita Y, Kojima K, Ohhashi R, et al. MiR-148a attenuates paclitaxel-resistance of hormone-refractory, drug-resistant prostate cancer PC3 cells by regulating MSK1 expression. J Biol Chem. 2010;285:19076–84.Google Scholar
- Leite KR, Sousa-Canavez JM, Reis ST, et al. Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis. Urol Oncol. 2010. doi:10.1016/j.urolonc.2009.02.002.Google Scholar
- Li J, Smyth P, Flavin R, et al. Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol. 2007;7:36.Google Scholar
- Lodes MJ, Caraballo M, Suciu D, et al. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One. 2009;4:e6229.Google Scholar
- Mattie MD, Benz CC, Bowers J, et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006;5:24.Google Scholar
- Poliseno L, Salmena L, Riccardi L, et al. Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal. 2010;3:ra29.Google Scholar