MicroRNA-30d inhibits the migration and invasion of human esophageal squamous cell carcinoma cells via the post‑transcriptional regulation of enhancer of zeste homolog 2

Xie,Rui; Wu,Shang-Nong; Gao,Cheng-Cheng; Yang,Xiao-Zhong; Wang,Hong‑Gang; Zhang,Jia-Ling; Yan,Wei; Ma,Tian-Heng

doi:10.3892/or.2017.5405

MicroRNA-30d inhibits the migration and invasion of human esophageal squamous cell carcinoma cells via the post‑transcriptional regulation of enhancer of zeste homolog 2

Authors:
- Rui Xie
- Shang-Nong Wu
- Cheng-Cheng Gao
- Xiao-Zhong Yang
- Hong‑Gang Wang
- Jia-Ling Zhang
- Wei Yan
- Tian-Heng Ma
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Affiliations: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: January 25, 2017 https://doi.org/10.3892/or.2017.5405
Pages: 1682-1690

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Abstract

The present study was carried out to investigate the expression pattern, clinical significance and biological functions of microRNA-30d (miR-30d) in esophageal carcinogenesis. Quantitative real-time PCR was performed to detect the expression levels of miR-30d in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. Then, associations between miR-30d expression and various clinicopathological features of patients with ESCC were statistically evaluated. In addition, the effects of miR-30d on the migration and invasion of two human ESCC cell lines transfected with miRNA or co-transfected with miRNA mimics and the expression vector of its target gene were determined. The results revealed that the expression levels of miR-30d were markedly decreased in ESCC tissues and cell lines, comparing with the corresponding normal controls. Notably, reduced expression of miR-30d occurred more frequently in ESCC patients with positive lymph node metastasis, moderate-poor differentiation and advanced tumor-node-metastasis stage than those with negative features. Functionally, enforced expression of miR-30d was found to inhibit cell invasion and migration of the ESCC cell lines. Luciferase reporter assay identified enhancer of zeste homolog 2 (EZH2) as a direct target gene of miR-30d. The expression level of EZH2 mRNA was negatively correlated with the expression of miR-30d in the ESCC tissues. Moreover, the inhibitory effect of miR-30d on ESCC cell motility was reversed by EZH2 overexpression. Collectively, these findings provide convincing evidence that decreased expression of miR-30d may be implicated in esophageal carcinogenesis and progression. We also confirmed miR-30d as a tumor-suppressor which may inhibit cancer cell motility by targeting EZH2, a potential therapeutic target for ESCC.

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