Alternative splicing of PSMD13 mediated by genetic variants is significantly associated with endometrial cancer risk

Accumulating evidence has shown that aberrant alternative splicing events are closely associated with the onset and development of cancer. However, whether genetic variants-associated alternative splicing is linked to risk of endometrial cancer remains largely uncertain.

We identified single nucleotide polymorphisms (SNPs) locates in the splicing number trait locus (sQTL) of endometrial cancer using the CancerSplicing QTL database. In parallel with bioinformatics analysis, we conducted a case-control study comprising 2,000 cases and 2,013 controls to assess the association between identified SNP which possesses mRNA splicing function and endometrial cancer susceptibility. Furthermore, we used the Kaplan-Meier Plotter, The Human Protein Atlas, SPNR, and Spliceman2 databases for sQTL and differential gene expression analyses to identify the genetic variant which most potentially influence the risk of endometrial cancer through alternative splicing to reveal the potential mechanism by which candidate SNPs regulate the risk of endometrial cancer.

The results indicated that SNP rs7128029 APSMD13 via regulating the exon skipping of PSMD13. When the rs7128029 allele was mutated from A to G, the expression of exon 2 of PSMD13 was markedly lower (p<0.001). Furthermore, compared with participants who had higher PSMD13 expression, those who had lower PSMD13 expression had shorter survival times.

These findings suggest that SNP rs7128029-mediated alternative splicing events in PSMD13 are associated with endometrial cancer risk and may be a potential early screening biomarker for endometrial cancer-susceptible populations.