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MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2

MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was signif...

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Autores principales: Guan, Hao, Li, Weiming, Li, Yuanyuan, Wang, Jichang, Li, Yan, Tang, Yanan, Lu, Shaoying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722343/
https://www.ncbi.nlm.nih.gov/pubmed/29220395
http://dx.doi.org/10.1371/journal.pone.0189490
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author Guan, Hao
Li, Weiming
Li, Yuanyuan
Wang, Jichang
Li, Yan
Tang, Yanan
Lu, Shaoying
author_facet Guan, Hao
Li, Weiming
Li, Yuanyuan
Wang, Jichang
Li, Yan
Tang, Yanan
Lu, Shaoying
author_sort Guan, Hao
collection PubMed
description MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer.
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spelling pubmed-57223432017-12-15 MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2 Guan, Hao Li, Weiming Li, Yuanyuan Wang, Jichang Li, Yan Tang, Yanan Lu, Shaoying PLoS One Research Article MicroRNAs (miRNAs) are important regulators of pathobiological processes in various cancer. In the present study, we demonstrated that miR-93 expression was significantly up-regulated in gastric cancer tissues compared with that in matched normal mucosal tissues. High expression of miR-93 was significantly associated with lymph node metastasis and tumor-node-metastasis (TNM) stage. Functionally, ectopic expression of miR-93 promoted cell proliferation, migration, invasion, EMT phenotypes, and repressed apoptosis and G1 cell cycle arrest in vitro, and promoted tumor formation in vivo. We further identified that tissue inhibitor of metalloproteinase 2 (TIMP2) was a direct target of miR-93 by using luciferase reporter assay, qRT-PCR, and immunoblotting assay. Furthermore, knockdown of TIMP2 with specific siRNA showed similar oncogenic effects in gastric cancer cells with that transfected with miR-93 mimics. Our findings indicated that miR-93 serves as a tumor promoter in human gastric carcinogenesis by targeting TIMP2, suggesting that miR-93 might be a promising biomarker and therapeutic target for treatment of gastric cancer. Public Library of Science 2017-12-08 /pmc/articles/PMC5722343/ /pubmed/29220395 http://dx.doi.org/10.1371/journal.pone.0189490 Text en © 2017 Guan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Guan, Hao
Li, Weiming
Li, Yuanyuan
Wang, Jichang
Li, Yan
Tang, Yanan
Lu, Shaoying
MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
title MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
title_full MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
title_fullStr MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
title_full_unstemmed MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
title_short MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2
title_sort microrna-93 promotes proliferation and metastasis of gastric cancer via targeting timp2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722343/
https://www.ncbi.nlm.nih.gov/pubmed/29220395
http://dx.doi.org/10.1371/journal.pone.0189490
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