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• W1864029557 abstract "Expression of vascular endothelial growth factor-A (VEGFA) by tumour-associated macrophages is critical for tumour progression and metastasis. Hypoxia, a common feature of the neoplastic microenvironment, induces VEGFA expression by increased transcription, translation, and mRNA stabilization. Here, we report a new mechanism of VEGFA regulation by hypoxia that involves reversal of microRNA (miRNA)-mediated silencing of VEGFA expression. We show that the CA-rich element (CARE) in the human VEGFA 3'-UTR is targeted by at least four miRNAs. Among these miRNAs, miR-297 and -299 are endogenously expressed in monocytic cells and negatively regulate VEGFA expression. Unexpectedly, hypoxia completely reverses miRNA-mediated repression of VEGFA expression. We show that heterogeneous nuclear ribonucleoprotein L (hnRNP L), which also binds the VEGFA 3'-UTR CARE, prevents miRNA silencing activity. Hypoxia induces translocation of nuclear hnRNP L to the cytoplasm, which markedly increases hnRNP L binding to VEGFA mRNA thereby inhibiting miRNA activity. In summary, we describe a novel regulatory mechanism in which the interplay between miRNAs and RNA-binding proteins influences expression of a critical hypoxia-inducible angiogenic protein. These studies may contribute to provide miRNA-based anticancer therapeutic tools." @default.
• W1864029557 created "2016-06-24" @default.
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• W1864029557 date "2011-02-22" @default.
• W1864029557 modified "2023-10-17" @default.
• W1864029557 title "Repression of VEGFA by CA-rich element-binding microRNAs is modulated by hnRNP L" @default.
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• W1864029557 doi "https://doi.org/10.1038/emboj.2011.38" @default.
• W1864029557 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3094116" @default.
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