Human Cancer Biology MicroRNA-202-3p Inhibits Cell Proliferation by Targeting ADP-Ribosylation Factor-like 5A in Human Colorectal Carcinoma

Purpose: MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of non–protein-coding RNAs. Here, we focused on the function and molecular mechanism of miR-202-3p and its potential clinical application in colorectal cancer. Experimental Design:miR-202-3p expression was determined by quantitative reverse transcriptase PCR (qRT-PCR) in 94 colorectal cancer tissues and corresponding noncancerous tissues (NCT).Cell proliferation and colony formation assays in vitro and xenograft experiments in vivowere used to evaluate the effect ofmiR202-3p on colorectal cancer cell proliferation. Luciferase assay andWestern blot analysis were performed to validate the potential targets of miR-202-3p after the preliminary screening by online prediction and microarray analysis. The mRNA and protein levels of target genes were detected by qRT-PCR and immunohistochemical staining. The copy number of pre-miR-202 was measured by quantitative PCR. Results: First, miR-202-3p was significantly downregulated in 46.7% colorectal cancer samples compared with NCTs. The overexpression of miR-202-3p inhibited colorectal cancer cell growth in vitro and repressed tumorigenesis in nude mice. Then, miR-202-3p downregulated ADP-ribosylation factor-like 5A (ARL5A) protein level bybinding to its 30 untranslated region, andknockdownofARL5Aphenocopied theproliferation inhibition effect of miR-202-3p. Furthermore, both of ARL5A mRNA and protein levels were upregulated in colorectal cancer samples compared with NCTs and high ARL5A protein levels predicted a poor prognosis. Conclusions: miR-202-3p might function as a tumor suppressor in colorectal cancer, and ARL5A, the functional target ofmiR-202-3p in colorectal cancer, is a potential prognostic factor for colorectal cancer.Clin Cancer Res; 20(5); 1–12. 2013 AACR.