HuR (ELAVL1) Stabilizes <i>SOX9</i> mRNA and Promotes Migration and Invasion in Breast Cancer Cells

RNA-binding proteins play diverse roles in cancer, influencing various facets of the disease, including proliferation, apoptosis, angiogenesis, senescence, invasion, epithelial–mesenchymal transition (EMT), and metastasis. HuR, a known RBP, is recognized for stabilizing mRNAs containing AU-rich elem...

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Bibliographic Details
Main Authors: Jesús Morillo-Bernal, Patricia Pizarro-García, Gema Moreno-Bueno, Amparo Cano, María J. Mazón, Pilar Eraso, Francisco Portillo
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/16/2/384
Description
Summary:RNA-binding proteins play diverse roles in cancer, influencing various facets of the disease, including proliferation, apoptosis, angiogenesis, senescence, invasion, epithelial–mesenchymal transition (EMT), and metastasis. HuR, a known RBP, is recognized for stabilizing mRNAs containing AU-rich elements (AREs), although its complete repertoire of mRNA targets remains undefined. Through a bioinformatics analysis of the gene expression profile of the Hs578T basal-like triple-negative breast cancer cell line with silenced HuR, we have identified SOX9 as a potential HuR-regulated target. SOX9 is a transcription factor involved in promoting EMT, metastasis, survival, and the maintenance of cancer stem cells (CSCs) in triple-negative breast cancer. Ribonucleoprotein immunoprecipitation assays confirm a direct interaction between HuR and <i>SOX9</i> mRNA. The half-life of <i>SOX9</i> mRNA and the levels of SOX9 protein decreased in cells lacking HuR. Cells silenced for HuR exhibit reduced migration and invasion compared to control cells, a phenotype similar to that described for SOX9-silenced cells.
ISSN:2072-6694