MiR‐15b‐5p inhibits castration‐resistant growth of prostate cancer cells by targeting the muscarinic cholinergic receptor CHRM3

Abstract

Cholinergic receptor muscarinic 3 (CHRM3)‐mediated focal adhesion kinase/YES‐associated protein (YAP) signalling is essential for the growth of castration‐resistant prostate cancer (CRPC) cells. Here, we evaluated the molecular mechanisms through which CHRM3 overexpression facilitates castration‐resistant growth. Small RNA sequencing combined with in silico analyses revealed that CHRM3 was a putative target of miR‐15b‐5p. Notably, androgen deprivation suppressed miR‐15b‐5p expression and increased CHRM3 expression. Moreover, miR‐15b‐5p bound directly to CHRM3 and inhibited YAP activation induced by CHRM3 stimulation. Furthermore, miR‐15b‐5p abolished the growth of CRPC cells induced by CHRM3 stimulation. We conclude that the miR‐15b‐5p/CHRM3/YAP signalling axis promotes the castration‐resistant growth of prostate cancer.