MicroRNA-337-3p suppresses cell viability, apoptosis, and autophagy by modulating PPARγ expression in androgen-dependent human prostate cancer

Abstract

We proposed that autophagy activated through PPARγ in prostate cancer could protect cancer against androgen deprivation. Our MTT and western blotting assay results showed that mimics of miR-337-3p repressed autophagy flux under androgen deprivation, whereas inhibitors had the opposite effect. Neither mimics nor inhibitors influenced cell motility and invasion. miR-337-3p downregulated PPARγ expression in dual luciferase reporter assays and promoted AMPK phosphorylation. The overexpression of PPARγ or AMPK agonists partly diminished the adverse influence of mimics on proliferation and cell autophagy. In a mouse xenograft model, tumors transplanted with LNCap cells having a miR-337-3p deficiency had a significantly larger volume and lower rate of apoptosis than in controls after orchidectomy. Our findings showed that the negative effects of miR-337-3p on cell survival after androgen deprivation through PPARγ degeneration and modulated autophagy could serve as a novel therapeutic target for androgen-dependent prostate cancer and provide a strategy against resistance to anti-androgen therapy.

KEYWORDS:

• MicroRNA-337-3p
• viability
• prostate cancer
• cell survival
• autophagy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.