Regulation of UHRF1 by microRNA-9 modulates colorectal cancer cell proliferation and apoptosis

Abstract

The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation, leading to decreased expressions of tumor suppressor genes and contributing to tumorigenesis. However, the factors that modulate UHRF1 expression in colorectal cancer (CRC) remain unclear. Here we showed that, compared with corresponding normal tissues, UHRF1 was upregulated and microRNA-9 (miR-9) was downregulated in CRC tissues. The expression of UHRF1 was inversely correlated with overall survival rates of patients with CRC. Overexpression of miR-9 in CRC cell lines significantly attenuated CRC cell proliferation and promoted cell apoptosis. The expression of UHRF1 was markedly reduced in pre-miR-9 transfected CRC cells. Using luciferase reporter assay, we confirmed that miR-9 was a direct upstream regulator of UHRF1. Finally, analysis of miR-9 and UHRF1 levels in human CRC tissues revealed that expression of miR-9 was inversely correlated with UHRF1 expression. Collectively, our results offer in vitro validation of the concept that miR-9 could repress the expression of UHRF1, and function as a tumor-suppressive microRNA in CRC. It may serve as a prognostic and therapeutic marker for CRC.