Cancers
SFPQ Promotes Hepatocellular Carcinoma Progression by Affecting GTF2H3 Splicing Variants
By Tang Q, Chen S, Chen X and 2 others.
Abstract
Background
Hepatocellular carcinoma (HCC), the predominant type of liver cancer, exhibits a high mortality rate due to unclear molecular mechanisms and limited biomarkers. Accumulating evidence indicates that splicing factors (SFs) can promote tumor cell proliferation, invasion, metastasis, and drug resistance by altering the splicing patterns of target genes. However, the regulatory mechanisms underlying SF-mediated alternative splicing (AS) are highly intricate, and the specific functions and pathways of SFs in HCC initiation and progression remain to be further elucidated.
Methods
First, Cox regression and LASSO regression analyses of splicing factors (SFs) were performed using the TCGA database, followed by validation using the ICGC dataset. The prognostic value of SFPQ was assessed with the Kaplan-Meier plotter. Next, the potential association of SFPQ with the immune microenvironment of HCC was explored using TIMER and CIBERSORT. In addition, we screened AS events associated with SFPQ expression in TCGA-LIHC, conducted GO/KEGG pathway enrichment analyses, and investigated the correlation between GTF2H3 percent spliced in index (PSI) values and clinicopathological features in HCC patients. Finally, the effect of targeting the exon 10- or exon 11-containing variants of GTF2H3 on HCC was examined at the cellular level.