Splicing Factor 3a Subunit 1 Promotes Colorectal Cancer Growth via Anti-programmed cell death of Syntaxin12.

RNA dysregulation mediated by abnormal RNA binding proteins (RBPs) is associated with tumorigenesis. However, the specific tumorigenic mechanisms of each RBP remained unclear. In this study, we demonstrate that splicing factor 3A1 (SF3A1) interacts to and stabilizes the mRNA of STX12, thereby inhibiting programmed cell death (PCD) in colorectal cancer cells. Downregulation of SF3A1 significantly inhibited cell growth in colorectal cancer cells, with minimal cytotoxicity observed in non-cancerous epithelial cells. We validated the tumor-promoting function of SF3A1 in an HCT116 transplanted mouse model. TUNEL staining and western blotting of PARP revealed SF3A1 inhibits PCD in colorectal cancer cells. A transcriptome analysis, combined with RNA-immunoprecipitation (IP), demonstrated that SF3A1 interact to and stabilized 144 mRNAs. Among these mRNAs, knockdown of STX12 (Syntaxin 12) in colorectal cancer cells inhibited cell growth but had no inhibitory effect on non-cancerous epithelial cells, HCEC-1CT. The mRNA levels of STX12 were significantly reduced upon downregulation of SF3A1, contributing to the inhibition of PCD in colorectal cancer cells. Therefore, SF3A1, which mediates STX12 mRNA stabilization, represents a promising therapeutic target for the treatment of colorectal cancer with fewer side effects.