SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner

作者：Xiaoyu Wang, Xiansheng Lu, Ping Wang, Qiaoyu Chen, Le Xiong, Minshan Tang, Chang Hong, Xiaowen Lin, Kaixi Shi, Li Liang, Jie Lin · 发表于：Journal of Translational Medicine · 年份：2022 · DOI：10.1186/s12967-022-03399-3 · 被引用次数：39 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、RNA Research and Splicing

BACKGROUND: Serine/arginine-rich splicing factor 9 (SRSF9) is a classical RNA-binding protein that is essential for regulating gene expression programs through its interaction with target RNA. Whether SRSF9 plays an essential role in colorectal cancer (CRC) progression and can serve as a therapeutic target is largely unknown. Here, we highlight new findings on the role of SRSF9 in CRC progression and elucidate the underlying mechanism. METHODS: CRC cell lines and clinical tissue samples were used. qRT-PCR, Western blotting, immunohistochemistry (IHC), gain- and loss-of-function assays, animal xenograft model studies, bioinformatic analysis, methylated single-stranded RNA affinity assays, gene-specific m6A quantitative qRT-PCR, dual-luciferase reporter assays and RNA stability assays were performed in this study. RESULTS: The expression level of SRSF9 was higher in CRC cell lines than that in an immortal human intestinal epithelial cell line. Overexpression of SRSF9 was positively associated with lymph node metastasis and Dukes stage. Functionally, SRSF9 promoted cell proliferation, migration and invasion in vitro and xenograft growth. The results of bioinformatic analysis indicated that DSN1 was the downstream target of SRSF9. In CRC cells and clinical tissue samples, the expression of SRSF9 was positively associated with the expression of DSN1. Knockdown of DSN1 partially inhibited the SRSF9-induced phenotype in CRC cells. Mechanistically, we further found that SRSF9 is an m...