High expression of serine and arginine-rich splicing factor 9 (SRSF9) is associated with hepatocellular carcinoma progression and a poor prognosis

Abstract

Background Serine and arginine-rich splicing factor 9 (SRSF9) has been linked to the occurrence and progression of various cancers; however, its effects and mechanism of action hepatocellular carcinoma (HCC) have not been reported. In this study, we used a bioinformatics approach and in vitro assays to evaluate the expression of SRSF9 in HCC, its prognostic value, and its underlying regulatory mechanisms, including analyses of related pathways and the role of methylation. Methods Transcriptomic and DNA methylation data for 357 HCC cases and 50 paratumor tissues in The Cancer Genome Atlas database were obtained. Additionally, protein expression data for cell lines and tissue samples were obtained from the Human Protein Atlas. The CMap databased was used to predict candidate drugs targeting SRSF9. Various cell lines were used for in vitro validation. Results SRSF9 expression was significantly elevated in HCC and was negatively regulated by its methylation site cg06116271. The low expression of SRSF9 and hypermethylation of cg06116271 were both associated with a longer overall survival time. A correlation analysis revealed ten genes that were co-expressed with SRSF9; levels of CDK4, RAN, DENR, RNF34, and ANAPC5 were positively correlated and levels of RBP4, APOC1, MASP2, HP, and HPX were negatively correlated with SRSF9 expression. The knockdown of SRSF9 in vitro inhibited the proliferation and migration of HCC cells and significantly reduced the expression of proteins in the Wnt signaling pathway (DVL2 and β-catenin) and cell cycle pathway (Cyclin D and Cyclin E). A CMap analysis identified two drugs, camptothecin and apigenin, able to target and inhibit the expression of SRSF9. Conclusions This study expands our understanding of the molecular biological functions of SRSF9 and cg06116271 and provides candidate diagnostic and therapeutic targets for HCC.

Differential expression profile of master regulators of gene expression- Serine-arginine rich splicing factor family in Oral Cancer

“…SRSF9 has also been implicated in cancers like hepatocellular carcinoma [22], colorectal cancer [23], and cervical cancer [24]. Frequent upregulation of SRSF10 in oral cancer has also been described earlier and it may have a role to play in its oncogenesis [25].…”

Allo: Accurate allocation of multi-mapped reads enables regulatory element analysis at repeats

“…Five datasets in this sample actually doubled their peak numbers after the inclusion of Allo including BRCA1, a well-known tumor suppressor gene 26 . In analyzing repetitive element family associations (Figure 7C), we also identified other TFs involved in cancer progression, including Jun 27 , ILK 28 , SRSF9 29 , and NCOA2 30 , that are highly associated with particular repeat families. Outside of Jun, none of these TFs have been previously identified as binding to repetitive elements.…”

Cisplatin-induced PANDAR-Chemo-EVs contribute to a more aggressive and chemoresistant ovarian cancer phenotype through the SRSF9-SIRT4/SIRT6 axis

“…SR proteins were found to regulate all levels of gene expression via transcription initiation and elongation, alternative splicing, mRNA stability, translation, and protein degradation [ 28 ]. The roles of SRSF9 were different in various pathologic-clinical subtype in cancer [ 29 30 31 ]. Recent pan-cancer analysis revealed that SRSF9 was upregulated in the proliferative subtype of OC and downregulated in the mesenchymal subtype of OC [ 32 ].…”