MicroRNA-146a (miR-146a) has been demonstrated as a tumour-suppressor in different malignancies including prostate cancer. As an endogenous small RNA, miR-146a regulates several gene expressions at the post-transcriptional level. Previous studies indicate that miR-146a is highly expressed in normal prostate tissue and significantly down-regulated in prostate cancer tissue and even worse in castration-resistant prostate cancer (CRPC) tissues. Over-expression of miR-146a in prostate cancer cell lines results in a marked reduction of cell proliferation, invasion and tumorigenesis. However, the regulating mechanism of miR-146a expression in the different stages of prostate cancer remains unclear. Yin Yang 1 (YY1), a critical regulator in prostate cancer development and progression, is predicted to be a direct target of miR-146a and binds to the promoter region of miR-146a, which is partly confirmed by the inverse expressions of miR-146a and YY1 in prostate cancer. Therefore, we hypothesize that YY1-miR-146a-YY1 regulatory circuitry contributes to prostate cancer and may serve as a future intervention target.