Inhibition of EZH2 Enhances the Antitumor Efficacy of Metformin in Prostate Cancer.

ABSTRACT: Upregulation of EZH2 is associated with advanced stage and poor prognosis of prostate cancer; therefore, it is likely to be a promising therapeutic target. Metformin, a drug that has been used to treat type 2 diabetes, was found to have antineoplastic activity in different cancers. Herein, we report that the combination of metformin and the EZH2 inhibitor GSK126 exerts synergistic inhibition on prostate cancer cell growth, both in vitro and in vivo Mechanistically, we identify that metformin can reduce EZH2 expression through upregulating miR-26a-5p, which is antagonized by androgen receptor (AR). Furthermore, we show that AR binds to the promoter of miR-26a-5p and suppresses its transcription. Although metformin can remove AR from the miR-26a-5p promoter, the interaction bet

SUBMITTER: Kong Y 

PROVIDER: S-EPMC7718407 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature