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MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer

Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms b...

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Autores principales: Shen, Jianjun, Niu, Weina, Zhou, Ming, Zhang, Hongbo, Ma, Jun, Wang, Ling, Zhang, Hongyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138091/
https://www.ncbi.nlm.nih.gov/pubmed/25136862
http://dx.doi.org/10.1371/journal.pone.0104510
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author Shen, Jianjun
Niu, Weina
Zhou, Ming
Zhang, Hongbo
Ma, Jun
Wang, Ling
Zhang, Hongyan
author_facet Shen, Jianjun
Niu, Weina
Zhou, Ming
Zhang, Hongbo
Ma, Jun
Wang, Ling
Zhang, Hongyan
author_sort Shen, Jianjun
collection PubMed
description Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post-transcriptional level, via a specific target site with the 3′UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410-transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer.
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spelling pubmed-41380912014-08-20 MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer Shen, Jianjun Niu, Weina Zhou, Ming Zhang, Hongbo Ma, Jun Wang, Ling Zhang, Hongyan PLoS One Research Article Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post-transcriptional level, via a specific target site with the 3′UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410-transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer. Public Library of Science 2014-08-19 /pmc/articles/PMC4138091/ /pubmed/25136862 http://dx.doi.org/10.1371/journal.pone.0104510 Text en © 2014 Shen 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shen, Jianjun
Niu, Weina
Zhou, Ming
Zhang, Hongbo
Ma, Jun
Wang, Ling
Zhang, Hongyan
MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer
title MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer
title_full MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer
title_fullStr MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer
title_full_unstemmed MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer
title_short MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer
title_sort microrna-410 suppresses migration and invasion by targeting mdm2 in gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138091/
https://www.ncbi.nlm.nih.gov/pubmed/25136862
http://dx.doi.org/10.1371/journal.pone.0104510
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