Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210...

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Autores principales: Ping Liu, Huiqiong Huang, Xiaorong Qi, Ce Bian, Meng Cheng, Lili Liu, Luqi Xue, Xia Zhao, Tao Yi, Yi Quan
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/fdaf1aef218a412284dcb9b5ce27d652
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spelling oai:doaj.org-article:fdaf1aef218a412284dcb9b5ce27d6522021-11-30T23:09:22ZHypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer2234-943X10.3389/fonc.2021.701488https://doaj.org/article/fdaf1aef218a412284dcb9b5ce27d6522021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.701488/fullhttps://doaj.org/toc/2234-943XLncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.Ping LiuHuiqiong HuangXiaorong QiCe BianMeng ChengLili LiuLuqi XueXia ZhaoTao YiYi QuanFrontiers Media S.A.articleovarian cancerMIR210HGHIF-1αhypoxiaprogressionNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic ovarian cancer
MIR210HG
HIF-1α
hypoxia
progression
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle ovarian cancer
MIR210HG
HIF-1α
hypoxia
progression
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Ping Liu
Huiqiong Huang
Xiaorong Qi
Ce Bian
Meng Cheng
Lili Liu
Luqi Xue
Xia Zhao
Tao Yi
Yi Quan
Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
description LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.
format article
author Ping Liu
Huiqiong Huang
Xiaorong Qi
Ce Bian
Meng Cheng
Lili Liu
Luqi Xue
Xia Zhao
Tao Yi
Yi Quan
author_facet Ping Liu
Huiqiong Huang
Xiaorong Qi
Ce Bian
Meng Cheng
Lili Liu
Luqi Xue
Xia Zhao
Tao Yi
Yi Quan
author_sort Ping Liu
title Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
title_short Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
title_full Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
title_fullStr Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
title_full_unstemmed Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
title_sort hypoxia-induced lncrna-mir210hg promotes cancer progression by inhibiting hif-1α degradation in ovarian cancer
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/fdaf1aef218a412284dcb9b5ce27d652
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AT taoyi hypoxiainducedlncrnamir210hgpromotescancerprogressionbyinhibitinghif1adegradationinovariancancer
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