Cyperotundone Promotes Chemosensitivity of Breast Cancer via SRSF1

Breast cancer is among the most common malignancies and the leading cause of cancer-related deaths in women. SRSF1 proteins belong to an important splicing factor (SF) family and bind to different splicing regulatory elements (SREs) to promote or inhibit splicing. Cyperotundone (CYT) is the major bioactive component of sedge and reported to exhibit multiple biological functions. This study aimed to investigate the effects of CYT on breast cancer drug resistance and to explore the molecular mechanisms. CYT significantly suppressed the in vitro and in vivo growth of BC cells without affect the normal cells, induced cell apoptosis, and inhibited the migration and invasion of drug-resistant BC. In comparison with the mono treatment with CYT, combination of CYT and doxrubicin (Dox) enhanced the effects. CYT treatment regulated the RNA and protein levels of epithelial mesenchymal transition (EMT) biomarkers, suppressed the sphere formation ability and expression of cancer stem cell biomarkers in drug resistant BC cells. Results from transcriptome sequencing analysis and experiments identified significantly decreased SRSF1 level in drug resistant cells after CYT treatment. Knockdown of SRSF1 significantly decreased expression of full-length MYO1B protein in drug-resistant BC cells. Overexpression of SRSF1 and MYO1B revered the inhibitory effects of CYT. In conclusion, CYT repressed the growth and metastasis of BC cells and recovered drug sensitivity, via regulating the alternative splicing of RNAs. Overall design: RNA-seq analysis of gene expression in human breast cancer cell line MDA-MB-231-DR, comparing control group with CYT treated.