Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis

MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tu...

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Main Authors: He, Jun, Jing, Yi, Li, Wei, Qian, Xu, Xu, Qing, Li, Feng-Shan, Liu, Ling-Zhi, Jiang, Bing-Hua, Jiang, Yue
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577861/
id pubmed-3577861
recordtype oai_dc
spelling pubmed-35778612013-02-22 Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis He, Jun Jing, Yi Li, Wei Qian, Xu Xu, Qing Li, Feng-Shan Liu, Ling-Zhi Jiang, Bing-Hua Jiang, Yue Research Article MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and miR-125b-inhibiting angiogenesis responses and Akt/p70S6K1/HIF-1α pathway. This study provides a rationale for new therapeutic approach to suppress tumor angiogenesis using miR-199a, miR-125b, or their mimics for ovarian cancer treatment in the future. Public Library of Science 2013-02-20 /pmc/articles/PMC3577861/ /pubmed/23437196 http://dx.doi.org/10.1371/journal.pone.0056647 Text en © 2013 He 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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author He, Jun
Jing, Yi
Li, Wei
Qian, Xu
Xu, Qing
Li, Feng-Shan
Liu, Ling-Zhi
Jiang, Bing-Hua
Jiang, Yue
spellingShingle He, Jun
Jing, Yi
Li, Wei
Qian, Xu
Xu, Qing
Li, Feng-Shan
Liu, Ling-Zhi
Jiang, Bing-Hua
Jiang, Yue
Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis
author_facet He, Jun
Jing, Yi
Li, Wei
Qian, Xu
Xu, Qing
Li, Feng-Shan
Liu, Ling-Zhi
Jiang, Bing-Hua
Jiang, Yue
author_sort He, Jun
title Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis
title_short Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis
title_full Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis
title_fullStr Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis
title_full_unstemmed Roles and Mechanism of miR-199a and miR-125b in Tumor Angiogenesis
title_sort roles and mechanism of mir-199a and mir-125b in tumor angiogenesis
description MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and miR-125b-inhibiting angiogenesis responses and Akt/p70S6K1/HIF-1α pathway. This study provides a rationale for new therapeutic approach to suppress tumor angiogenesis using miR-199a, miR-125b, or their mimics for ovarian cancer treatment in the future.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577861/
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