EAU 2017: Special session of the Prostate Cancer Prevention Group - Risk factors and biomarkers for screening and triage: The role of miRNA in oncogenesis and progression

London, England (UroToday.com) MicroRNAs (miRNAs) are single stranded, non-coding RNAs with 18-22 nucleotides. Currently there are 1881 precursors and 2588 mature human miRNAs described. They act as post transcriptional regulators and regulate approximately 30% of human mRNAs. One miRNA can regulate numerous genes and one gene can be regulated by different miRNAs. miRNAs have tissue specific expression and function and they are involved in a variety of pathological and oncogenic pathways. They were first diagnosed in 1993 and Andrew Z. Fire and Craig C. Mello received a noble prize for their discovery of "RNA interference – gene silencing by double-stranded RNA"

miRNA differential expression and functions include chromosomal loss or gain or mutation,
epigenetic silencing (e.g. by promoter hypermethylation), constitutive promoter activation, altered regulation by deregulated transcriptional factors, altered processing due to enzyme alterations, and they can have altered binding sites in target mRNA.

miRNA expression profiling by microarray analyses has been done in prostate cancer. Additionally comparison of malignant and non-malignant prostate tissues has been performed as well. There is s potential association of miRNA to TNM, Gleason score and prognosis in prostate cancer. Identification of putative target-genes and affected pathways has been sought. It is known that the miRNAs miR115a/16, -21, -25, -34, -106, -125b, -141/200, -143, -145, -205, -221/222, and -375 are frequently altered in prostate cancer.

The regulation of the androgen receptor (AR) expression, which has a crucial role in the carcinogenesis of primary prostate cancer and development of castration resistant prostate cancer, is performed through various miRNAs. It has been shown that AR induced overexpression of miRNA-21 is associated with prostate cancer progression and chemoresistance (through inhibition of PTEN and TGF beta pathway). The miRNA -221/222 confer androgen independent cell growth. miRNAs also have a proven role in bone metastasis in prostate cancer. Due to the stability of miRNAS, its strong association to prostate cancer, and due to the fact that it is possible to perform quantitation of miRNAs in blood, urine and tissue, it has a significant potential of being used as a biomarker for prostate cancer.

There are also long non-coding RNAs (IncRNAs) with regulatory function in a multitude of cellular processes. It has been shown that there is dysregulation of IncRNAs in different diseases. A large German research consortium named RIBOLUTION is involved in the search for prostate cancer associated biomarkers, including these new class of regulating RNAs.

In conclusion, miRNAs regulate several prostate cancer related pathways – cancer onset, recurrence, progression, metastasis and therapy resistance. miRNAs are stable in biomaterials and easy to asses, and can be used as biomarkers. IncRNAs are a new class of regulating RNAs that can also serve as potential biomarkers. Future aims should include expanding the knowledge of “RNA world” and understanding the multiple levels of regulatory mechanisms in cancer.

Presented by: Dr. Manfred Wirth, Dresden (DE)

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto

Twitter: @GoldbergHanan

at the #EAU17 -March 24-28, 2017- London, England

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