Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, PR China.
Center for Experimental Medical Research, Third Xiangya Hospital, Central South University, Changsha, PR China.
Dig Liver Dis. 2019 Mar;51(3):397-411. doi: 10.1016/j.dld.2018.08.021. Epub 2018 Aug 30.
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.
胆管癌（CCA）是一种致命性恶性肿瘤，死亡率高，诊断困难。最近，由于其在肿瘤治疗方面的潜在应用价值，microRNAs（miRs）受到了广泛的研究。
本研究旨在探讨 miR-494 是否影响 CCA 的上皮间质转化（EMT）、肿瘤生长和转移。
预测 WDHD1 在 CCA 表达芯片中的调控 miRNAs，然后测定正常胆管细胞组织和 CCA 组织中 miR-494 和 WDHD1 的表达。测定相关蛋白水平。随后检测 CCA 细胞迁移、侵袭、活力和细胞周期分布，以及 miR-494 对 CCA 细胞生长的剂量依赖性作用。最后，测量肿瘤发生和淋巴结转移（LNM）。
最初，miR-194 通过负向调控 WDHD1 和 miR-494 影响 CCA 的发展，而 miR-494 在 CCA 中下调，而 WDHD1 上调。此外，miR-494 过表达增加了 E-钙粘蛋白的表达，同时降低了 WDHD1、N-钙粘蛋白、波形蛋白、Snail、Twist 和 MMP-9 的表达。最后，观察到过表达的 miR-494 抑制 EMT、细胞活力、迁移、侵袭、阻止细胞周期进程、肿瘤形成和 LNM，同时促进体内细胞凋亡。
本研究表明，miR-494 通过抑制 WDHD1 在 CCA 中过表达，抑制 EMT、肿瘤形成和 LNM，同时促进 CCA 细胞凋亡。
