A novel regulatory circuit of miR-152 and DNMT1 in human bladder cancer

Abstract

Downregulation of microRNA-152 (miR-152) has been observed in various types of human malignancies, including Bladder cancer (BC). However, the role of miR-152 in the development and progression of BC is still unclear. In our previous study, we identified a functional crosstalk between miR-152 and DNA methyltransferase 1 (DNMT1) involved in Nis-induced malignant transformation. In the present study, we found that the expression of miR-152 was specifically downregulated in BC cells and tissues via the DNA hypermethylation of the miR-152 promoter. The overexpression of miR-152 in BC cells resulted in a reduction of DNMT1, whereas the inhibition of the expression of miR-152 induced an elevated level of DNMT1. Further studies revealed that miR-152 directly downregulated the expression of DNMT1 by targeting the 3'-UTR of its transcript in BC cells. In addition, ectopic expression of miR-152 in BC cells significantly inhibited cell proliferation, whereas the inhibition of miR-152 expression led to increased cell proliferation. These findings indicated a novel regulatory circuit of miR-152/DNMT1 in BC, and more importantly, the combination of miR-152 and DNMT1 may function as promising therapeutic modalities and early biomarkers for BC.