ONCOmmunity

microRNA-202-3p inhibits cell proliferation by targeting ADP-ribosylation factor-like 5A in human colorectal carcinoma.

By: Qifeng Wang, Zhaohui Huang, Weijie Guo, Shujuan Ni, Xiuying Xiao, Lisha Wang, Dan Huang, Cong Tan, Qinghua Xu, Ruopeng Zha, Jiwei Zhang, Weiqi Sheng, Xianghuo He, Xiang Du

Authors' Affiliations: Department of Pathology; bioMérieux Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College; Institute of Pathology; Institutes of Biomedical Sciences, Fudan University, Shanghai; Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine; and Department of Oncology, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.
2013-12-10; doi: 10.1158/1078-0432.CCR-13-1023

Abstract

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

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 vivo were used to evaluate the effect of miR-202-3p on colorectal cancer cell proliferation. Luciferase assay and Western 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 by binding to its 3' untranslated region, and knockdown of ARL5A phenocopied the proliferation 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 of miR-202-3p in colorectal cancer, is a potential prognostic factor for colorectal cancer.