Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer.
Knockdown of m6A Reader IGF2BP3 Inhibited Hypoxia-Induced Cell Migration and Angiogenesis by Regulating Hypoxia Inducible Factor-1α in Stomach Cancer.
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DOI：
10.3389/fonc.2021.711207
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发表时间：
2021
影响因子：
4.7
通讯作者：
Wen H
中科院分区：
文献类型：
--
作者：
Jiang L;Li Y;He Y;Wei D;Yan L;Wen H
缺氧是包括胃癌在内的实体瘤的共同特征，并且与癌症恶性进展密切相关。N6-甲基腺苷（m6 A）是RNA上的一种常见修饰，参与调节癌症中的RNA命运和缺氧反应。然而，m6 A阅读器胰岛素样生长因子-II mRNA结合蛋白3（IGF 2BP 3）和SC缺氧微环境之间的相互作用还不清楚。本研究通过生物信息学分析、RT-qPCR和western blot检测IGF 2BP 3和缺氧诱导因子-1 α（HIF 1A）的表达水平。通过Transwell和伤口愈合试验评估细胞迁移能力。血管生成的潜力进行了评价VEGF分泌，管形成，和鸡胚绒毛尿囊膜（CAM）测定。IGF 2BP 3和HIF 1A之间的相互作用进行了探讨，使用生物信息学分析和RIP和荧光素酶报告基因测定。结果表明，IGF 2BP 3和HIF 1A在SC组织和缺氧处理的SC细胞中高表达。IGF 2BP 3基因敲低可抑制SC中缺氧诱导的细胞迁移和血管生成。IGF 2BP 3通过直接结合SC细胞中HIF 1A mRNA编码区中的特异性m6 A位点而正调控HIF 1A表达。结论：IGF 2BP 3基因敲低可通过下调HIF 1A的表达抑制低氧诱导的细胞迁移和血管生成。
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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影响因子：
2
作者：
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通讯作者：
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作者：
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4.3
作者：
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