MicroRNA-143 acts as a tumor suppressor by targeting hexokinase 2 in human prostate cancer

Am J Cancer Res. 2015 May 15;5(6):2056-63. eCollection 2015.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in cancer progression through regulating gene expression. Down-regulation of miR-143 has been reported in a number of cancers. However, the biological functions of miR-143 in prostate cancer remain largely unexplored. In this study, we showed that miR-143 expression was reduced in approximately 62.5% of the specimens examined. By loss-of-function and gain-of-function studies in human prostate cancer PC-3 cells, we demonstrated that miR-143 has an inhibitory effect on cell proliferation as evidenced by decreased cell viability, increased cell apoptosis and cell cycle arrest at the G1/S transition. Furthermore, we identified hexokinase 2 (HK2), a metabolic enzyme that executes the first step of aerobic glycolysis, as a target of miR-143 in prostate cancer. Knockdown of HK2 recapitulated the effects of miR-143 and accompanied with decreased glucose metabolism. Taken together, these data indicate that miR-143/HK2 axis plays an important role in the development of prostate cancer and represents a potential therapeutic target for prostate cancer.

Keywords: growth; hexokinase 2; miR-143; prostate cancer.