SF3A3 Drives Tumorigenesis in Endometrial Cancer by Enhancing c-FOS Expression and Represents a Potential Therapeutic Target

Aberrant expression of splicing factors is increasingly recognized as a critical driver of cancer progression. Herein, we unravel SF3A3, a core component of the spliceosome, being highly expressed in endometrial cancer (EC) and playing an oncogenic role by driving splicing alterations, and consequently promoting tumor progression and therapeutic resistance. Mechanistically, We found through RIP seq data that SF3A3 could specifically bind to a series of genes, including c-FOS. Subsequent experiments have confirmed that SF3A3 coud regulate the alternative splicing of c-FOS, an anti-apoptotic gene implicated in resistance to cisplatin, a first-line chemotherapeutic agent for EC. SF3A3 facilitates the inclusion of exons 2 and 3 in c-FOS, resulting in the production of full-length c-FOS, which promotes tumor progression and cisplatin resistance. Overall design: We overexpressed GFP-SF3A3 in KLE cells and extracted RNA bound to SF3A3 protein through IP experiments, which were then sent for RNA seq sequencing Antibodies used in this study: anti-SF3A3 (Cell Signaling Technology, catalog number ab157194) anti-GFP (Proteintech, catalog number 66002-1-Ig) [Used for wb] GFP beads(AlpalifeBio, catalog number ktsm1301) [Used for RIP-seq]