MicroRNA-198 suppresses prostate tumorigenesis by targeting MIB1

MicroRNAs are small non-coding RNA molecules which act as modulators of gene function, and have been identified as playing important roles in cancer as both tumor suppressors and oncogenes. The present study aimed to examine the role of miR-198 in prostate cancer aggression by analyzing how it influences several hallmarks of cancer. Abundance of miR-198 in prostate cancer and association with clinical characteristics was analyzed using a CPC-Gene prostate cancer dataset. Overexpression of miR-198 was performed using transient transfection of miR-198 mimic prior to assaying proliferation, cell cycle, and colony formation in LNCaP and DU145 cell lines using standard protocols. In vivo tumor formation in athymic nude mice was examined using LNCaP xenografts with stable overexpression conferred using lentiviral miR-198 transduction. Protein and mRNA abundance of MIB1 was determined using western blotting and RT-qPCR respectively, while miR-198 binding to MIB1 was validated using a luciferase reporter assay. miR-198 abundance was lower in high Gleason grade prostate cancer relative to intermediate and low-grade cancer. Overexpression of miR-198 diminished proliferation of prostate cancer cell lines, increased G0/G1 cell cycle arrest, and significantly impaired colony formation. Elevated miR-198 abundance was also demonstrated to impair tumor formation in vivo using LNCaP xenografts. Mindbomb E3 ubiquitin protein ligase 1 (MIB1) was demonstrated to be directly targeted by miR-198, and knockdown of MIB1 recapitulated the effects of miR-198 on proliferation and colony formation. The present evidence supports miR-198 as an important tumor suppressor in prostate cancer, and demonstrates for the first time that it acts by targeting MIB1. The present study reinforces the importance and complexity of miRNA in regulating prostate cancer aggression.