Srsf9-KO Mouse

Srsf9, also known as serine/arginine-rich splicing factor 9, is a classical RNA-binding protein essential for regulating gene expression programs [2]. It is involved in processes like alternative splicing, which is a crucial post-transcriptional regulatory mechanism [4]. Srsf9 can interact with target RNAs, influencing the splicing of various genes and thereby participating in multiple biological pathways related to cell growth, apoptosis, and disease-related processes [2,4]. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying Srsf9's functions.

In cardiac hypertrophy, Mettl1-catalyzed m7G modification of Srsf9 mRNA increases Srsf9 expression. This in turn facilitates alternative splicing and stabilization of NFATc4, promoting cardiac hypertrophy. Knockdown of Srsf9 protects against TAC-or Mettl1-induced cardiac hypertrophic phenotypes in vivo and in vitro [1]. In colorectal cancer, Srsf9 promotes cell proliferation, migration, and invasion, and its overexpression is associated with lymph node metastasis and Dukes stage. Srsf9 binds to DSN1 mRNA in an m6A-related manner, stabilizing it, and knockdown of DSN1 eliminates the effects of Srsf9 overexpression [2]. In glioblastoma, Srsf9 promotes cell proliferation and migration by binding to the promoter of CDK1 and increasing its transcription level [3]. In oral cancer, Srsf9 mediates oncogenic RNA splicing of SLC37A4 via liquid-liquid phase separation, promoting cancer progression and contributing to cisplatin chemotherapy resistance [5]. In ovarian cancer, a positive feedback loop of Srsf9/USP22/ZEB1 promotes cancer progression, and knockdown of Srsf9 suppresses the malignant phenotypes of ovarian cancer cells [6]. In colorectal cancer, inhibition of Srsf9 enhances the sensitivity to erastin-induced ferroptosis by reducing glutathione peroxidase 4 expression [7].

In summary, Srsf9 plays essential roles in multiple biological processes, especially in disease-related pathways such as cardiac hypertrophy, cancer progression, and response to ferroptosis. Findings from KO-like models have revealed its functions in these disease areas, providing potential therapeutic targets for related diseases.

References:

1. Yu, Shuting, Sun, ZhiYong, Ju, Tiantian, Yang, Baofeng, Du, Weijie. 2024. The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9-Mediated Splicing of NFATc4. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2308769. doi:10.1002/advs.202308769. https://pubmed.ncbi.nlm.nih.gov/38810124/

2. Wang, Xiaoyu, Lu, Xiansheng, Wang, Ping, Liang, Li, Lin, Jie. 2022. SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner. In Journal of translational medicine, 20, 198. doi:10.1186/s12967-022-03399-3. https://pubmed.ncbi.nlm.nih.gov/35509101/

3. Luo, Chunyuan, He, Juan, Yang, Yang, Liu, Wenrong, Peng, Yong. 2024. SRSF9 promotes cell proliferation and migration of glioblastoma through enhancing CDK1 expression. In Journal of cancer research and clinical oncology, 150, 292. doi:10.1007/s00432-024-05797-0. https://pubmed.ncbi.nlm.nih.gov/38842611/

4. Ha, Jiyeon, Jang, Hana, Choi, Namjeong, Zheng, Xuexiu, Shen, Haihong. 2021. SRSF9 Regulates Cassette Exon Splicing of Caspase-2 by Interacting with Its Downstream Exon. In Cells, 10, . doi:10.3390/cells10030679. https://pubmed.ncbi.nlm.nih.gov/33808656/

5. Peng, Qiu, Wang, Lujuan, Long, Ying, Liao, Qianjin, Zhou, Yujuan. 2025. SRSF9 mediates oncogenic RNA splicing of SLC37A4 via liquid-liquid phase separation to promote oral cancer progression. In Journal of advanced research, , . doi:10.1016/j.jare.2025.03.013. https://pubmed.ncbi.nlm.nih.gov/40064440/

6. Wang, Jing, Hu, Ming, Min, Jie, Li, Xin. 2024. A positive feedback loop of SRSF9/USP22/ZEB1 promotes the progression of ovarian cancer. In Cancer biology & therapy, 25, 2427415. doi:10.1080/15384047.2024.2427415. https://pubmed.ncbi.nlm.nih.gov/39530604/

7. Wang, Rui, Su, Qi, Yin, Hongzhuan, Lv, Chi, Yan, Zhaopeng. 2021. Inhibition of SRSF9 enhances the sensitivity of colorectal cancer to erastin-induced ferroptosis by reducing glutathione peroxidase 4 expression. In The international journal of biochemistry & cell biology, 134, 105948. doi:10.1016/j.biocel.2021.105948. https://pubmed.ncbi.nlm.nih.gov/33609745/