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

MiR-15b-5p 通过靶向毒蕈碱胆碱能受体 CHRM3 抑制前列腺癌细胞的去势抵抗性生长

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作者:Shunichi Asai, Yusuke Goto, Kengo Tanigawa, Yuya Tomioka, Mayuko Kato, Keiko Mizuno, Shinichi Sakamoto, Naohiko Seki

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.

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