Bo Liu1, Yu Hu2, Lu Qin3, Xu-Bin Peng4, Ya-Xun Huang5. 1. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, PR China. 2. Center for Experimental Medical Research, Third Xiangya Hospital, Central South University, Changsha, PR China. 3. Department of Intestinal Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China. 4. Department of Neurosurgery, The Cancer Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, PR China. 5. Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, PR China. Electronic address: hyxhuangyaxun@126.com.
Abstract
BACKGROUND: 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. AIMS: The current study was aimed to investigate whether miR-494 influences epithelial-mesenchymal transition (EMT), tumor growth and metastasis of CCA. METHODS: 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. RESULTS: 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. CONCLUSION: This study indicated that miR-494 overexpression suppresses EMT, tumor formation and LNM while promoting CCA cell apoptosis through inhibiting WDHD1 in CCA.
BACKGROUND: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. AIMS: The current study was aimed to investigate whether miR-494 influences epithelial-mesenchymal transition (EMT), tumor growth and metastasis of CCA. METHODS: 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. RESULTS: 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. CONCLUSION: This study indicated that miR-494 overexpression suppresses EMT, tumor formation and LNM while promoting CCA cell apoptosis through inhibiting WDHD1 in CCA.
Authors: Ayse Ertay; Huiquan Liu; Dian Liu; Ping Peng; Charlotte Hill; Hua Xiong; David Hancock; Xianglin Yuan; Marcin R Przewloka; Mark Coldwell; Michael Howell; Paul Skipp; Rob M Ewing; Julian Downward; Yihua Wang Journal: Cell Death Dis Date: 2020-11-21 Impact factor: 8.469