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miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer

MicroRNAs are endogenously expressed, small non-coding RNAs that regulate gene expression by targeting mRNAs for translational repression or degradation. Our previous studies indicated that miR-874 played a suppressive role in gastric cancer (GC) development and progression. However, the role of miR...

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Autores principales: Zhang, Xiaoyu, Tang, Jie, Zhi, Xiaofei, Xie, Kunling, Wang, Weizhi, Li, Zheng, Zhu, Yi, Yang, Li, Xu, Hao, Xu, Zekuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359318/
https://www.ncbi.nlm.nih.gov/pubmed/25596740
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author Zhang, Xiaoyu
Tang, Jie
Zhi, Xiaofei
Xie, Kunling
Wang, Weizhi
Li, Zheng
Zhu, Yi
Yang, Li
Xu, Hao
Xu, Zekuan
author_facet Zhang, Xiaoyu
Tang, Jie
Zhi, Xiaofei
Xie, Kunling
Wang, Weizhi
Li, Zheng
Zhu, Yi
Yang, Li
Xu, Hao
Xu, Zekuan
author_sort Zhang, Xiaoyu
collection PubMed
description MicroRNAs are endogenously expressed, small non-coding RNAs that regulate gene expression by targeting mRNAs for translational repression or degradation. Our previous studies indicated that miR-874 played a suppressive role in gastric cancer (GC) development and progression. However, the role of miR-874 in tumor angiogenesis and the mechanisms underlying its function in GC remained to be clarified. Here, gain- and loss-of-function assays demonstrated that miR-874 inhibited the tumor angiogenesis of GC cells in vitro and in vivo. Through reporter gene and western blot assays, STAT3 was shown to be a direct target of miR-874. Overexpression of STAT3 rescued the loss of tumor angiogenesis caused by miR-874. Conversely, the STAT3-shRNA attenuated the increased tumor angiogenesis caused by the miR-874-inhibitor. Furthermore, the levels of miR-874 were inversely correlated with those of STAT3 protein in GC tissues. Taken together, these findings indicate that down-regulation of miR-874 contributes to tumor angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a target for human GC therapy.
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spelling pubmed-43593182015-03-26 miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer Zhang, Xiaoyu Tang, Jie Zhi, Xiaofei Xie, Kunling Wang, Weizhi Li, Zheng Zhu, Yi Yang, Li Xu, Hao Xu, Zekuan Oncotarget Research Paper MicroRNAs are endogenously expressed, small non-coding RNAs that regulate gene expression by targeting mRNAs for translational repression or degradation. Our previous studies indicated that miR-874 played a suppressive role in gastric cancer (GC) development and progression. However, the role of miR-874 in tumor angiogenesis and the mechanisms underlying its function in GC remained to be clarified. Here, gain- and loss-of-function assays demonstrated that miR-874 inhibited the tumor angiogenesis of GC cells in vitro and in vivo. Through reporter gene and western blot assays, STAT3 was shown to be a direct target of miR-874. Overexpression of STAT3 rescued the loss of tumor angiogenesis caused by miR-874. Conversely, the STAT3-shRNA attenuated the increased tumor angiogenesis caused by the miR-874-inhibitor. Furthermore, the levels of miR-874 were inversely correlated with those of STAT3 protein in GC tissues. Taken together, these findings indicate that down-regulation of miR-874 contributes to tumor angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a target for human GC therapy. Impact Journals LLC 2015-01-22 /pmc/articles/PMC4359318/ /pubmed/25596740 Text en Copyright: © 2015 Zhang et al. http://creativecommons.org/licenses/by/2.5/ 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 credited
spellingShingle Research Paper
Zhang, Xiaoyu
Tang, Jie
Zhi, Xiaofei
Xie, Kunling
Wang, Weizhi
Li, Zheng
Zhu, Yi
Yang, Li
Xu, Hao
Xu, Zekuan
miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
title miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
title_full miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
title_fullStr miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
title_full_unstemmed miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
title_short miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer
title_sort mir-874 functions as a tumor suppressor by inhibiting angiogenesis through stat3/vegf-a pathway in gastric cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359318/
https://www.ncbi.nlm.nih.gov/pubmed/25596740
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