HuR Stabilizes ISOX9/I mRNA and Promotes Migration and Invasion in Breast Cancer Cells

RNA-binding proteins (RBPs) play a critical role in controlling gene expression post-transcriptionally and their dysregulation can lead to various diseases, including cancer. One such RBP is HuR, whose levels have been associated with a poor clinical prognosis in breast cancer. Nevertheless, the precise molecular mechanism underlying this connection remains incompletely characterized. Our study uncovers that HuR targets SOX9 mRNA in breast cancer cells and provides compelling evidence supporting HuR’s involvement in cell migration and invasion. 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 SOX9 mRNA. The half-life of SOX9 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.