Srsf12, a member of the serine-arginine rich splicing factor (SRSF) family, is involved in regulating RNA metabolism, specifically pre-mRNA constitutive and alternative splicing [3]. It may play a role in multiple biological processes as it has been associated with various pathways such as the PI3K-AKT and Jak-STAT signaling pathways [1].

In pancreatic cancer, Srsf12 knockout (KO) in Kras-mutated mice (KrasG12DSrsf12fl/fl and Srsf12fl/flPdx1cre) showed that depletion of Srsf12 accelerated Kras-driven pancreatic tumorigenesis and enhanced tumor innervation. Mechanistically, SRSF12 inhibits neurite outgrowth by generating a LAMA3 splice isoform lacking the fourth and fifth LG (G45) domains, and G45 promotes tumor innervation by activating ITGB1 and FAK in neurons [2]. In acute myeloid leukemia (AML), SRSF12 is highly expressed and is an independent predictor of favorable prognosis. Enrichment analysis showed its involvement in PI3K-AKT and Jak-STAT signaling pathways, and its expression was positively correlated with helper T cell infiltration but negatively correlated with neutrophil and macrophage infiltration [1].

In conclusion, Srsf12 is a significant splicing factor involved in RNA splicing and has implications in disease-related biological processes. The Srsf12 KO mouse model in pancreatic cancer reveals its role as a suppressor of tumor innervation and pancreatic tumorigenesis, while in AML, its high expression is associated with prognosis and immune cell infiltration, providing insights into disease mechanisms and potential diagnostic and therapeutic targets.

References:

1. Zhang, MengMeng, Tan, YuanYuan, Xie, ZhiBin, Wang, Meng, Li, JiaJia. 2024. SRSF12 is a prognostic biomarker involved in immune infiltration in acute myeloid leukemia. In Hematology (Amsterdam, Netherlands), 29, 2420301. doi:10.1080/16078454.2024.2420301. https://pubmed.ncbi.nlm.nih.gov/39463061/

2. Yang, Min-Wei, Jia, Qin-Yuan, Xu, Da-Peng, Sun, Yong-Wei, Liu, Wei. 2025. SRSF12 deficiency enhances tumor innervation and accelerates pancreatic tumorigenesis. In Cancer letters, 616, 217563. doi:10.1016/j.canlet.2025.217563. https://pubmed.ncbi.nlm.nih.gov/39986371/

3. More, Dhanashree Anil, Kumar, Arun. 2020. SRSF3: Newly discovered functions and roles in human health and diseases. In European journal of cell biology, 99, 151099. doi:10.1016/j.ejcb.2020.151099. https://pubmed.ncbi.nlm.nih.gov/32800280/