Androgen receptor (AR) signaling plays a critical role in prostate cancer (PCA) pathogenesis. Yet, the regulation of AR signaling remains elusive. Even with stringent androgen deprivation therapy, AR signaling persists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31 and AR signaling. We examined primary and metastatic PCA and found that miR-31 expression was reduced as a result of promoter hypermethylation and importantly, the levels of miR-31 expression was inversely correlated with the aggressiveness of the disease. As the expression of AR and miR-31 was inversely correlated in the cell lines, our study further suggested that miR-31 and AR could mutually repress each other. Upregulation of miR-31 effectively suppressed AR expression through multiple mechanisms and inhibited PCA growth in vivo. Notably, we found that miR-31 targeted AR directly at a site located in the coding region, which was commonly mutated in PCA. Additionally, miR-31 suppressed cell cycle regulators, including E2F1, E2F2, EXO1, FOXM1, and MCM2. Together, our findings suggest a novel AR regulatory mechanism mediated through miR-31 expression. The downregulation of miR-31 may disrupt cellular homeostasis and contribute to the evolution and progression of PCA. We provide implications for epigenetic treatment and support clinical development of detecting miR-31 promoter methylation as a novel biomarker.

This large national database study demonstrates that thoracoscopic lobectomy is associated with fewer in-hospital postoperative complications compared with open lobectomy. Thoracoscopic lobectomy appears to be applicable to the wider general thoracic surgical community.

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