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Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA‐21
Author(s) -
He Qian,
Cai Lei,
Shuai Ling,
Li Dajiang,
Wang Cheng,
Liu Yongkang,
Li Xiaowu,
Li Zhihua,
Wang Shuguang
Publication year - 2013
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.21859
Subject(s) - pten , gene knockdown , biology , microrna , transfection , cell growth , cancer research , immunohistochemistry , downregulation and upregulation , apoptosis , microbiology and biotechnology , gene , immunology , genetics , pi3k/akt/mtor pathway
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. © 2011 Wiley Periodicals, Inc.