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MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression
BACKGROUND: MicroRNA-381 (miR-381) has been reported to play suppressive or promoting roles in different malignancies. However, the expression level, biological function, and underlying mechanisms of miR-381 in gastric cancer remain poorly understood. Our previous study indicated that transmembrane...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307754/ https://www.ncbi.nlm.nih.gov/pubmed/28193228 http://dx.doi.org/10.1186/s13046-017-0499-z |
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author | Cao, Qinghua Liu, Fang Ji, Kaiyuan Liu, Ni He, Yuan Zhang, Wenhui Wang, Liantang |
author_facet | Cao, Qinghua Liu, Fang Ji, Kaiyuan Liu, Ni He, Yuan Zhang, Wenhui Wang, Liantang |
author_sort | Cao, Qinghua |
collection | PubMed |
description | BACKGROUND: MicroRNA-381 (miR-381) has been reported to play suppressive or promoting roles in different malignancies. However, the expression level, biological function, and underlying mechanisms of miR-381 in gastric cancer remain poorly understood. Our previous study indicated that transmembrane protein 16A (TMEM16A) contributed to migration and invasion of gastric cancer and predicted poor prognosis. In this study, we found that miR-381 inhibited the metastasis of gastric cancer through targeting TMEM16A expression. METHODS: MiR-381 expression was analyzed using bioinformatic software on open microarray datasets from the Gene Expression Omnibus (GEO) and confirmed by quantitative RT-PCR (qRT-PCR) in human gastric cancer tissues and cell lines. Cell proliferation was investigated using MTT and cell count assays, and cell migration and invasion abilities were evaluated by transwell assay. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Luciferase reporter assay, western blot, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were employed to explore the mechanisms of the effect of miR-381 on gastric cancer cells. RESULTS: MiR-381 was significantly down-regulated in gastric cancer tissues and cell lines. Low expression of miR-381 was negatively related to lymph node metastasis, advanced tumor stage and poor prognosis. MiR-381 decreased gastric cancer cell proliferation, migration and invasion in vitro and in vivo. TMEM16A was identified as a direct target of miR-381 and the expression of miR-381 was inversely correlated with TMEM16A expression in gastric cancer tissues. Combination analysis of miR-381 and TMEM16A revealed the improved prognostic accuracy for gastric cancer patients. Moreover, miR-381 inhibited TGF-β signaling pathway and down-regulated epithelial–mesenchymal transition (EMT) phenotype partially by mediating TMEM16A. CONCLUSIONS: MiR-381 may function as a tumor suppressor by directly targeting TMEM16A and regulating TGF-β pathway and EMT process in the development of progression of gastric cancer. MiR-381/TMEM16A may be a novel therapeutic candidate target in gastric cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-017-0499-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5307754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53077542017-02-22 MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression Cao, Qinghua Liu, Fang Ji, Kaiyuan Liu, Ni He, Yuan Zhang, Wenhui Wang, Liantang J Exp Clin Cancer Res Research BACKGROUND: MicroRNA-381 (miR-381) has been reported to play suppressive or promoting roles in different malignancies. However, the expression level, biological function, and underlying mechanisms of miR-381 in gastric cancer remain poorly understood. Our previous study indicated that transmembrane protein 16A (TMEM16A) contributed to migration and invasion of gastric cancer and predicted poor prognosis. In this study, we found that miR-381 inhibited the metastasis of gastric cancer through targeting TMEM16A expression. METHODS: MiR-381 expression was analyzed using bioinformatic software on open microarray datasets from the Gene Expression Omnibus (GEO) and confirmed by quantitative RT-PCR (qRT-PCR) in human gastric cancer tissues and cell lines. Cell proliferation was investigated using MTT and cell count assays, and cell migration and invasion abilities were evaluated by transwell assay. Xenograft nude mouse models were used to observe tumor growth and pulmonary metastasis. Luciferase reporter assay, western blot, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were employed to explore the mechanisms of the effect of miR-381 on gastric cancer cells. RESULTS: MiR-381 was significantly down-regulated in gastric cancer tissues and cell lines. Low expression of miR-381 was negatively related to lymph node metastasis, advanced tumor stage and poor prognosis. MiR-381 decreased gastric cancer cell proliferation, migration and invasion in vitro and in vivo. TMEM16A was identified as a direct target of miR-381 and the expression of miR-381 was inversely correlated with TMEM16A expression in gastric cancer tissues. Combination analysis of miR-381 and TMEM16A revealed the improved prognostic accuracy for gastric cancer patients. Moreover, miR-381 inhibited TGF-β signaling pathway and down-regulated epithelial–mesenchymal transition (EMT) phenotype partially by mediating TMEM16A. CONCLUSIONS: MiR-381 may function as a tumor suppressor by directly targeting TMEM16A and regulating TGF-β pathway and EMT process in the development of progression of gastric cancer. MiR-381/TMEM16A may be a novel therapeutic candidate target in gastric cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-017-0499-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-13 /pmc/articles/PMC5307754/ /pubmed/28193228 http://dx.doi.org/10.1186/s13046-017-0499-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Cao, Qinghua Liu, Fang Ji, Kaiyuan Liu, Ni He, Yuan Zhang, Wenhui Wang, Liantang MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression |
title | MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression |
title_full | MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression |
title_fullStr | MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression |
title_full_unstemmed | MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression |
title_short | MicroRNA-381 inhibits the metastasis of gastric cancer by targeting TMEM16A expression |
title_sort | microrna-381 inhibits the metastasis of gastric cancer by targeting tmem16a expression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307754/ https://www.ncbi.nlm.nih.gov/pubmed/28193228 http://dx.doi.org/10.1186/s13046-017-0499-z |
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