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Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer

Hypoxia is a common feature of solid tumors including stomach cancer (SC) and is closely associated with cancer malignant progression. N6-methyladenosine (m6A), a common modification on RNA, is involved in the regulation of RNA fate and hypoxic responses in cancers. However, the interaction between...

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Autores principales: Jiang, Libin, Li, Yingxia, He, Yixin, Wei, Dapeng, Yan, Lvyin, Wen, Hongtao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490730/
https://www.ncbi.nlm.nih.gov/pubmed/34621671
http://dx.doi.org/10.3389/fonc.2021.711207
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author Jiang, Libin
Li, Yingxia
He, Yixin
Wei, Dapeng
Yan, Lvyin
Wen, Hongtao
author_facet Jiang, Libin
Li, Yingxia
He, Yixin
Wei, Dapeng
Yan, Lvyin
Wen, Hongtao
author_sort Jiang, Libin
collection PubMed
description Hypoxia is a common feature of solid tumors including stomach cancer (SC) and is closely associated with cancer malignant progression. N6-methyladenosine (m6A), a common modification on RNA, is involved in the regulation of RNA fate and hypoxic responses in cancers. However, the interaction between m6A reader insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) and SC hypoxic microenvironment is poorly defined. In the present study, expression levels of IGF2BP3 and hypoxia inducible factor-1α (HIF1A) were examined by bioinformatics analysis and RT-qPCR and western blot assays. Cell migratory ability was assessed through Transwell and wound healing assays. The angiogenic potential was evaluated by VEGF secretion, tube formation, and chick embryo chorioallantoic membrane (CAM) assays. The interaction between IGF2BP3 and HIF1A was explored using bioinformatics analysis and RIP and luciferase reporter assays. The results showed that IGF2BP3 and HIF1A were highly expressed in SC tissues and hypoxia-treated SC cells. IGF2BP3 knockdown inhibited hypoxia-induced cell migration and angiogenesis in SC. IGF2BP3 positively regulated HIF1A expression by directly binding to a specific m6A site in the coding region of HIF1A mRNA in SC cells. HIF1A overexpression abrogated the effects of IGF2BP3 knockdown on hypoxia-induced cell migration and angiogenesis in SC. In conclusion, IGF2BP3 knockdown inhibited hypoxia-induced cell migration and angiogenesis by down-regulating HIF1A in SC.
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spelling pubmed-84907302021-10-06 Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer Jiang, Libin Li, Yingxia He, Yixin Wei, Dapeng Yan, Lvyin Wen, Hongtao Front Oncol Oncology Hypoxia is a common feature of solid tumors including stomach cancer (SC) and is closely associated with cancer malignant progression. N6-methyladenosine (m6A), a common modification on RNA, is involved in the regulation of RNA fate and hypoxic responses in cancers. However, the interaction between m6A reader insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) and SC hypoxic microenvironment is poorly defined. In the present study, expression levels of IGF2BP3 and hypoxia inducible factor-1α (HIF1A) were examined by bioinformatics analysis and RT-qPCR and western blot assays. Cell migratory ability was assessed through Transwell and wound healing assays. The angiogenic potential was evaluated by VEGF secretion, tube formation, and chick embryo chorioallantoic membrane (CAM) assays. The interaction between IGF2BP3 and HIF1A was explored using bioinformatics analysis and RIP and luciferase reporter assays. The results showed that IGF2BP3 and HIF1A were highly expressed in SC tissues and hypoxia-treated SC cells. IGF2BP3 knockdown inhibited hypoxia-induced cell migration and angiogenesis in SC. IGF2BP3 positively regulated HIF1A expression by directly binding to a specific m6A site in the coding region of HIF1A mRNA in SC cells. HIF1A overexpression abrogated the effects of IGF2BP3 knockdown on hypoxia-induced cell migration and angiogenesis in SC. In conclusion, IGF2BP3 knockdown inhibited hypoxia-induced cell migration and angiogenesis by down-regulating HIF1A in SC. Frontiers Media S.A. 2021-09-21 /pmc/articles/PMC8490730/ /pubmed/34621671 http://dx.doi.org/10.3389/fonc.2021.711207 Text en Copyright © 2021 Jiang, Li, He, Wei, Yan and Wen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Jiang, Libin
Li, Yingxia
He, Yixin
Wei, Dapeng
Yan, Lvyin
Wen, Hongtao
Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer
title Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer
title_full Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer
title_fullStr Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer
title_full_unstemmed Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer
title_short Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer
title_sort knockdown of m6a reader igf2bp3 inhibited hypoxia-induced cell migration and angiogenesis by regulating hypoxia inducible factor-1α in stomach cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490730/
https://www.ncbi.nlm.nih.gov/pubmed/34621671
http://dx.doi.org/10.3389/fonc.2021.711207
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