MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma
MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma
复制标题
DOI：
10.1016/j.dld.2018.08.021
复制
发表时间：
2019-03-01
影响因子：
4.5
通讯作者：
Huang, Ya-Xun
中科院分区：
文献类型：
--
作者：
Liu, Bo;Hu, Yu;Huang, Ya-Xun
背景：胆管癌是一种恶性肿瘤，其特点是死亡率高，诊断困难。近年来，microRNAs（miRs）因其在肿瘤治疗中的潜在作用而受到广泛关注，本研究旨在探讨miR-494对CCA上皮间质转化（EMT）、肿瘤生长和转移的影响。预测CCA表达芯片中WDHD 1的调控miRNAs，然后测定正常胆管细胞组织和CCA组织中miR-494和WDHD 1的表达。测定相关蛋白水平。随后检测CCA细胞的迁移、侵袭、存活和细胞周期分布以及miR-494对CCA细胞生长的剂量依赖性影响。结果：miR-194通过下调WDHD 1和miR-494的表达而上调WDHD 1的表达，从而影响CCA的发生发展。此外，miR-494过表达增加了E-cadherin的表达，同时降低了WDHD 1、N-cadherin、Vimentin、Snail、Twist和MMP-9的表达。结论：miR-494过表达可抑制CCA细胞的EMT、肿瘤形成和LNM，并通过抑制CCA中的WDHD 1而促进CCA细胞凋亡。(C)2018年意大利胃肠病学杂志由爱思唯尔有限公司出版。保留所有权利。
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. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.