MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma.

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective. The current study was aimed to investigate whether miR-494 influences epithelial-mesenchymal transition (EMT), tumor growth and metastasis of CCA. The regulatory miRNAs of WDHD1 in CCA expression chip were predicted, followed by determination of the miR-494 and WDHD1 expression in normal cholangiocyte tissues and CCA tissues. The related protein levels were determined. CCA cell migration, invasion, viability, and cell cycle distribution and the dosage-dependent effect of miR-494 on CCA cell growth were subsequently detected. Finally, tumorigenicity and lymph node metastasis (LNM) were measured. Initially, miR-194 affected the CCA development via negatively regulating WDHD1 and miR-494 which were downregulated while WDHD1 was upregulated in CCA. In addition, miR-494 overexpression elevated E-cadherin expression while decreased expressions of WDHD1, N-cadherin, Vimentin, Snail, Twist and MMP-9. Finally, overexpressed miR-494 was observed to suppress EMT, cell viability, migration, invasion, arrest cell cycle progression, tumor formation, and LNM while accelerating cell apoptosis in vivo. This study indicated that miR-494 overexpression suppresses EMT, tumor formation and LNM while promoting CCA cell apoptosis through inhibiting WDHD1 in CCA.

Liu B ，Hu Y ，Qin L ，Peng XB ，Huang YX ... -  《-》

MicroRNA-21 regulates biological behavior by inducing EMT in human cholangiocarcinoma.

Liu Z ，Jin ZY ，Liu CH ，Xie F ，Lin XS ，Huang Q ... -  《International Journal of Clinical and Experimental Pathology》

Tetraspanin 1 promotes epithelial-to-mesenchymal transition and metastasis of cholangiocarcinoma via PI3K/AKT signaling.

Wang Y ，Liang Y ，Yang G ，Lan Y ，Han J ，Wang J ，Yin D ，Song R ，Zheng T ，Zhang S ，Pan S ，Liu X ，Zhu M ，Liu Y ，Cui Y ，Meng F ，Zhang B ，Liang S ，Guo H ，Liu Y ，Hassan MK ，Liu L ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Upregulated microRNA-194 impairs stemness of cholangiocarcinoma cells through the Rho pathway via inhibition of ECT2.

Cholangiocarcinoma (CCA) is devastating for its delayed presence, difficulty in diagnosis, and high mortality. Other studies have supported the important role of microRNAs (miRNAs) in the pathogenesis of CCA, and the role of miR-194 was investigated in several human cancers, though, the molecular mechanism of miR-194 in CCA stem cells remains largely unknown. We aimed to identify the functional significance of miR-194 in CCA. The microarray-based analysis was applied to detect the epithelial cell transforming sequence 2 (ECT2) expression and predict the miRNA-regulated ECT2, followed by the identification of relationship between ECT2 and obtained miRNA by dual-luciferase reporter gene assay. The effects of depletion or ectopic expression of miR-194 on Rho pathway and the biological characteristics of CCA were assessed by reverse transcription quantitative polymerase chain reaction, immunoblotting, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, scratch test, Transwell, and flow cytometry. Lastly, tumor growth was assessed by xenograft tumor in nude mice. ECT2 was highly expressed while miR-194 was poorly expressed in CCA stem cells, and the targeting relation between ECT2 and miR-194 was proved. More important, the elevated expression of miR-194 or ECT2 silencing inhibited the Rho pathway, and further promoted the apoptosis and suppressed the stem cell proliferation, migration, and invasion of CCA in vitro. miR-194 inhibited the tumor growth in vivo. In a word, miR-194 inhibits ECT2 and blocks the activation of Rho signaling pathway, thus promoting apoptosis, inhibiting proliferation and migration of CCA stem cells, and suppressing tumor growth. The mechanism can be regarded as a target for treating CCA.

Gao J ，Dai C ，Yu X ，Yin XB ，Zhou F ... -  《-》

Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122.

Zhu H ，Mi Y ，Jiang X ，Zhou X ，Li R ，Wei Z ，Jiang H ，Lu J ，Sun X ... -  《-》