Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA-21.

Abstract

Due to the lack of effective diagnostic tools, most patients with cholangiocarcinoma (CCA) have no chance of surgical resection. Ars2 is a protein that was reported to be important for microRNA (miR) biogenesis, and its depletion can reduce the levels of several miRs, including miR-21, which is overexpressed in CCAs. We hypothesized that Ars2 was also present in CCAs and could be an early diagnostic marker. In our experiments, Ars2, PTEN, PDCD4, and miR-21 were evaluated in 18 CCAs and paired normal tissues. ShArs2, miR-21 mimics, and Ars2 were transfected into CCA and bile duct epithelial cells either alone or together. Cell proliferation, tumorigenicity analysis and expression changes of Ars2, PTEN, PDCD4, and miR-21 were evaluated. We found that both Ars2 and miR-21 were overexpressed, with 95% sensitivity and 100% specificity, and an ROC of 0.995 in distinguishing between CCAs and paired normal tissues by qRT-PCR. PTEN and PDCD4 were reversed in immunohistochemistry, but no difference was observed using qRT-PCR. The knockdown of Ars2 in CCA cells decreased the level of miR-21, inhibited cell proliferation and prevented tumor formation in nude mice. Ars2 knockdown also led to an increase in both PTEN and PDCD4 protein levels. Both proteins decreased when the miR-21 mimic was con-transfected. However, the overexpression of Ars2 alone could not get the opposite results. Based on our data, we conclude that Ars2 is overexpressed in human CCA and may be a diagnostic marker. Ars2 depletion increases PTEN and PDCD4 protein levels via the reduction of miR-21.

DOI: 10.1002/mc.21859
020406020132014201520162017
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@article{He2013Ars2IO, title={Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA-21.}, author={Qian He and Lei Cai and Ling Shuai and Dajiang Li and Cheng Wang and Yongkang Liu and Xiaowu Li and Zhihua Li and Shuguang Wang}, journal={Molecular carcinogenesis}, year={2013}, volume={52 4}, pages={286-96} }