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 andSOX9mRNA. The half-life ofSOX9mRNA 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.
RNA结合蛋白在癌症中扮演多种角色，影响包括增殖、凋亡、血管生成、衰老、侵袭、上皮-间质转化（EMT）及转移在内的疾病多个方面。HuR作为一种已知的RNA结合蛋白，因其能稳定含有AU富集元件（AREs）的mRNA而广受认可，但其完整的mRNA靶标谱尚未完全明确。通过对HuR沉默的Hs578T基底样三阴性乳腺癌细胞系基因表达谱进行生物信息学分析，我们鉴定出SOX9是HuR潜在调控靶点。SOX9是一种在三阴性乳腺癌中参与促进EMT、转移、存活及维持癌症干细胞（CSCs）特性的转录因子。核糖核蛋白免疫沉淀实验证实了HuR与SOX9 mRNA之间存在直接相互作用。在HuR缺失的细胞中，SOX9 mRNA的半衰期及SOX9蛋白水平均显著下降。与对照细胞相比，HuR沉默的细胞表现出迁移和侵袭能力减弱，这一表型与SOX9沉默细胞中观察到的现象相似。
HuR (ELAVL1) StabilizesSOX9mRNA and Promotes Migration and Invasion in Breast Cancer Cells
肿瘤(癌症)患者之家