Dataset Information

MicroRNA-17/20a impedes migration and invasion via TGF-?/ITGB6 pathway in esophageal squamous cell carcinoma.

ABSTRACT: Patients with esophageal squamous cell carcinoma (ESCC) have an overall poor prognosis due to invasion and metastasis. Although it has been studied extensively, the metastatic mechanisms of ESCC remains largely unclear. Here, we evaluated microRNA expression in ESCC cell sublines with distinct motility and found that microRNA-17 and microRNA-20a (miR-17/20a) dramatically impeded cell migration and invasion of ESCC in vitro and decreased pulmonary arrest in vivo. Furthermore, we identified that TGF-? receptor 2 (TGFBR2) and Smad anchor for receptor activation (SARA) served as genuine miR-17/20a targets, which are both implicated in TGF-? pathway. TGF-? treatment promoted the motility of ESCC cells, and miR-17/20a could attenuate the activation of TGF-? pathway by weakening the phosphorylation of Smad2/3 to reduce the expression of ITGB6, which was crucial in migration and invasion of ESCC cells. Moreover, evaluation of ESCC specimens revealed a close correlation between miR-17/20a, TGFBR2, SARA and lymph node metastasis. Together, our findings demonstrate that miR-17/20a suppresses cell migration and invasion of ESCC by modulating TGF-?/ITGB6 pathway, suggesting a promising strategy for diagnosis and therapy of ESCC invasion and metastasis.

SUBMITTER: Jing C

PROVIDER: S-EPMC4969404 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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MicroRNA-17/20a impedes migration and invasion via TGF-β/ITGB6 pathway in esophageal squamous cell carcinoma.

Jing Chao C Ma Gang G Li Xukun X Wu Xiaowei X Huang Furong F Liu Kuangyu K Liu Zhihua Z

American journal of cancer research 20160701 7

Patients with esophageal squamous cell carcinoma (ESCC) have an overall poor prognosis due to invasion and metastasis. Although it has been studied extensively, the metastatic mechanisms of ESCC remains largely unclear. Here, we evaluated microRNA expression in ESCC cell sublines with distinct motility and found that microRNA-17 and microRNA-20a (miR-17/20a) dramatically impeded cell migration and invasion of ESCC in vitro and decreased pulmonary arrest in vivo. Furthermore, we identified that T ...[more]

PMID: 27508097

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Project description:Despite investigations into microRNA (miRNA) expression in esophageal cancer (EC) tissue, miRNAs that participate in EC pathogenesis and their subsequent mechanisms of action remain to be determined. The present study aimed to identify important miRNAs that contribute to EC development, and to assess miRNA biomarkers that could be used in EC diagnosis, prognosis and therapy. Bioinformatics analysis was performed to reanalyze EC tissue miRNA expression microarray dataset GSE113776, which was followed by in vitro verification of miRNA functions using reverse transcription?quantitative PCR, western blot analysis and a dual?luciferase reporter assay. Out of 93 miRNAs extracted, only miR?200a was significantly increased in EC tissues. Transfection of KYSE150 esophageal squamous cell carcinoma (ESCC) cells with miR?200a mimics significantly increased their proliferative, migratory and invasive ability, whereas the opposite cell behaviors were observed in ESCC cells transfected with a miR?200a inhibitor. A total of six miR?200a target genes [catenin ?1 (CTNNB1), cadherin?1 (CDH1), PTEN, adenomatous polyposis coli (APC), catenin ?1 (CTNNA1) and superoxide dismutase 2 (SOD2)] were selected for further analysis based on Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein?protein interaction network map data and protein expression in esophageal tissue. These target genes were downregulated under miR?200a expression and upregulated in the presence of the miR?200a inhibitor. The association between miR?200a and the 3'?untranslated region of target genes in ESCC cells was confirmed using a dual?luciferase reporter assay. In conclusion, the present study demonstrated that miR?200a may participate in the promotion of ESCC cell proliferation, migration and invasion, and provided novel evidence for the direct interaction between miR?200a and CTNNB1, CDH1, PTEN, APC, CTNNA1 and SOD2, which may contribute to the observed altered cell behavior.

Dataset Information

MicroRNA-17/20a impedes migration and invasion via TGF-?/ITGB6 pathway in esophageal squamous cell carcinoma.

Publications

MicroRNA-17/20a impedes migration and invasion via TGF-β/ITGB6 pathway in esophageal squamous cell carcinoma.

Similar Datasets

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