MicroRNA-455 inhibits proliferation and invasion of colorectal cancer by targeting RAF proto-oncogene serine/threonine-protein kinase.

Abstract

Colorectal cancer (CRC, also known as colon cancer, rectal cancer, or bowel cancer) is the second leading cause of cancer mortality in the Western world. MicroRNAs (miRNAs) are a class of small (18-25 nucleotides long) noncoding RNAs with important posttranscriptional regulatory functions. miRNAs play important roles in various physiological and pathological processes including carcinogenesis in various solid cancers including CRC. In order to investigate the roles that miRNAs played in CRC, the expression of human miRNAs (in 20 normal adjacent tissue samples and 20 colon cancer samples) was examined in this study. miR-455, miR-484, and miR-101 were significantly downregulated in colon cancer samples. And overexpression of miR-455 significantly inhibited the proliferation and the invasion of SW480, but had no effect on apoptosis. PCR and Western blot showed that overexpression of miR-455 decreased protein expression of RAF proto-oncogene serine/threonine-protein kinase (RAF1) but had no effect on mRNA level. Luciferase assay indicated that miR-455 regulated RAF1 expression directly. Moreover, overexpression of RAF1 partially reversed the inhibitory effect of miR-455 on the growth and the invasion of SW480. The data indicated that miR-455 regulates the proliferation and invasion of colorectal cancer cells, at least in part, by downregulating RAF1, a direct target of miR-455. Collectively, our study demonstrated that miR-455-RAF1 may represent a new potential therapeutic target for colorectal carcinoma treatment.