SF3B6 promotes the cellular proliferation by extensively interacting with and regulating transcripts expression and alternative splicing in MDA-MB-231 cells [RIP-seq]
SF3B6 functions as a splicing factor, and is closely associated with the malignant progression of multiple cancer types, including breast cancer. However, its underlying mechanism is largely unknown. In this study, we investigated the molecular mechanism of SF3B6 in MDA-MB-231 cells by transfection with siRNA of SF3B6 combined with high-throughput transcriptome sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq) technology. We found siSF3B6 significantly repressed cellular proliferation level. Downstream RNA-seq analysis revealed that SF3B6 silencing resulted in widespread changes in differentially expressed genes (DEGs) and regulatory alternative splicing events (RASEs) that are involved in inflammatory response and immune regulatory pathways, such as the NF-?B signaling pathway. iRIP-seq analysis indicated that SF3B6 regulates gene expression and alternative splicing by directly interacting with target mRNA. Further analysis showed that SF3B6 potentially contributes to the malignant properties of TNBC by regulating the expression and splicing of key oncogenes including PPM1F and FASN, and tumor suppressor genes, including RLF and RECQL4. This study highlights the crucial role of SF3B6 in TNBC, providing new insights into its potential as a biomarker or therapeutic target in breast diagnosis and treatment in future. Overall design: We investigated the molecular mechanism of SF3B6 in MDA-MB-231 cells by transfection with siRNA of SF3B6  combined with high-throughput transcriptome sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq) technology. RNA-seq experiments were performed with three biological replicates for siSF3B6 and siNC. The iRIP-seq experiments were performed with two biological replicates for SF3B6 and Input.