MiR-448 suppresses E2F3 to inhibit proliferation and induce apoptosis in human colorectal cancer cells

Abstract

Background: Colorectal cancer (CRC) is one of the most common malignancies over the world, and recent studies have demonstrated that microRNAs are implicated in the carcinogenesis of CRC. Here we analyzed the expression of miR-448 in CRC tumor samples and studied its function and mechanism in regulating proliferation and apoptosis in CRC cells. Methods: Thirty-four paired CRC tissues and normal adjacent tissues were analyzed for miR-448 and E2F3 expression using Real-time PCR. Endogenous miR-448 was modulated by transfection of miR-448 mimics or inhibitor. Cell proliferation was determined by cell viability assay and BrdU proliferation assay. Changes of apoptosis after miR-448 transfection were determined by caspase-3 activity assay, TUNEL assay and western blot assay for cleaved-PARP expression. Luciferase reporter assay was used to validate whether miR-448 targets E2F3. Results: We found that miR-448 expression was significantly down-regulated in CRC tissues, which is constantly associated with up-regulation of E2F3 expression. Overexpression of miR-448 in CRC cell line restricted cell proliferation and induced apoptosis, whereas inhibition of miR-448 had opposite effects on cell proliferation and apoptosis. E2F3 functions as a direct target of miR-448, and overexpression of E2F3 cancelled the effects of miR-448 on cell proliferation and apoptosis. Conclusions: We conclude that miR-448 is downregulated in CRC and functions to suppress tumor cell growth by targeting E2F3, and miR-448 could be a potential therapeutic target for CRC.