Role of miR-2909 in Prostate Carcinogenesis

Abstract

The biggest challenge in prostate cancer treatment is to understand the signaling mecha- nisms controlling disease progression. In this context, microRNAs assume huge importance and have recently become an attractive area of research. MicroRNAs are naturally occurring, single-stranded, small non-coding RNAs of 19–25 nucleotides that regulate gene expression. MicroRNAs function as oncogenes or tumor-suppressor genes, and their deregulation is a common feature of human cancers including prostate cancer. Among deregulated microRNAs in prostate cancer, some microRNAs are directly under androgen receptor signaling control and function as the effectors of androgen signaling. Recent findings have shown that apoptosis antagonizing transcription factor (AATF) gene encodes a microRNA designated as miR-2909 that plays an important role in prostate cancer progression. miR-2909 is identified as an androgen-regulated microRNA acting as a novel effector of androgen/androgen receptor signaling. It enhances the proliferation potential of prostate cancer cells and assists in prostate cancer survival under reduced androgen levels by maintaining a positive feedback loop with AR. miR-2909 exerts its oncogenic effects via multiple mechanisms including attenuation of tumor-suppressive effects of TGFβ signaling by directly targeting TGFBR2 and via STAT1 pathway and upregulation of ISGylation pathway through SOCS3/STAT1 pathway.