title: 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.
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.
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Shang-Nong
authors.initials: SN
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Tian-Heng
authors.initials: TH
authors.lastname: Ma
mesh_terms: D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein