# Splicing Factor 3a Subunit 1 Promotes Colorectal Cancer Growth via Anti-Apoptotic Effects of Syntaxin12

## TL;DR

This study shows that SF3A1 promotes colorectal cancer growth by stabilizing STX12 mRNA and preventing cell death.

## Contribution

The novel contribution is identifying SF3A1 and STX12 as a regulatory axis promoting colorectal cancer progression through anti-apoptotic effects.

## Key findings

- SF3A1 knockdown suppresses CRC cell proliferation with minimal effect on non-cancerous cells.
- SF3A1 inhibits apoptosis in CRC cells by stabilizing STX12 mRNA.
- STX12 knockdown induces apoptosis in CRC cells but not in non-cancerous epithelial cells.

## Abstract

RNA dysregulation mediated by aberrant RNA-binding proteins (RBPs) is closely associated with tumorigenesis. However, the tumorigenic mechanisms of each RBP remained unclear. In this study, we demonstrate that downregulation of Splicing factor 3A1 (SF3A1) markedly suppressed the proliferation of colorectal cancer (CRC) cells, with minimal cytotoxicity observed in non-cancerous epithelial cells. The tumor-promoting function of SF3A1 was further validated in an HCT116 xenograft mouse model. Multiple apoptosis assays—including TdT-mediated dUTP nick end labeling (TUNEL) staining, poly-ADP-ribose polymerase (PARP) immunoblotting, and caspase-3/7 activity measurements—showed that SF3A1 inhibited apoptotic signaling in CRC cells. Transcriptome analysis, combined with RNA-immunoprecipitation (RIP), identified Syntaxin 12 (STX12) as a downstream effector of SF3A1. Knockdown of STX12 induced apoptosis in CRC cells but had no effect on the viability of non-cancerous HCEC-1CT epithelial cells. Furthermore, STX12 mRNA levels were significantly reduced following SF3A1 knockdown, indicating that SF3A1-mediated stabilization of STX12 contributes to apoptosis resistance in CRC cells. Collectively, our findings establish that SF3A1 promotes CRC progression by stabilizing STX12 mRNA and selectively inhibiting apoptosis in malignant cells, thereby identifying the SF3A1–STX12 regulatory axis as a novel and selective therapeutic target for CRC.