SF3B6 promotes the oncogenic phenotypes of MDA-MB-231 cells by extensively interacting with and regulating transcripts expression and alternative splicing.

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 breast tumor cells. In this study, we investigated the molecular mechanism and downstream targets of SF3B6 by transfecting the siRNA of SF3B6 (siSF3B6) into MDA-MB-231 cells and combining with high-throughput transcriptome sequencing (RNA-seq) and improved RNA immunoprecipitation sequencing (iRIP-seq) technology. We found siSF3B6 significantly repressed cellular proliferation and migration levels, but increased apoptosis levels of MDA-MB-231 cells. Downstream RNA-seq analysis revealed that SF3B6 silencing resulted in widespread changes in differentially expressed genes (DEGs) and regulatory alternative splicing events (RASEs) that were involved in inflammatory response and immune regulatory pathways, such as the NF-κB signaling pathway. The iRIP-seq analysis indicated that SF3B6 can regulate the gene expression and alternative splicing profile by directly interacting with its targeting mRNAs. 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, which were validated by RT-qPCR experiment. In summary, this study highlights the crucial molecular role of SF3B6 in breast cancer cells, providing new insights into its potential as a biomarker or valuable target in breast cancer diagnosis and treatment in future.