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

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.

He Q ，Cai L ，Shuai L ，Li D ，Wang C ，Liu Y ，Li X ，Li Z ，Wang S ... -  《-》

PTEN and PDCD4 are bona fide targets of microRNA-21 in human cholangiocarcinoma.

Liu CZ ，Liu W ，Zheng Y ，Su JM ，Li JJ ，Yu L ，He XD ，Chen SS ... -  《-》

Overexpression of microRNA-21 regulating PDCD4 during tumorigenesis of liver fluke-associated cholangiocarcinoma contributes to tumor growth and metastasis.

Chusorn P ，Namwat N ，Loilome W ，Techasen A ，Pairojkul C ，Khuntikeo N ，Dechakhamphu A ，Talabnin C ，Chan-On W ，Ong CK ，Teh BT ，Yongvanit P ... -  《-》

MicroRNA-144 suppresses cholangiocarcinoma cell proliferation and invasion through targeting platelet activating factor acetylhydrolase isoform 1b.

Yang R ，Chen Y ，Tang C ，Li H ，Wang B ，Yan Q ，Hu J ，Zou S ... -  《BMC CANCER》

MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3.

Selaru FM ，Olaru AV ，Kan T ，David S ，Cheng Y ，Mori Y ，Yang J ，Paun B ，Jin Z ，Agarwal R ，Hamilton JP ，Abraham J ，Georgiades C ，Alvarez H ，Vivekanandan P ，Yu W ，Maitra A ，Torbenson M ，Thuluvath PJ ，Gores GJ ，LaRusso NF ，Hruban R ，Meltzer SJ ... -  《-》