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SRSF6 -regulated alternative splicing of genes involved in DNA repair is associated with prostate cancer progression

ABSTRACT: Alternative splicing (AS) occurs in nearly all human genes and abnormal AS has a close connection with cancer. SRSF6, a canonical member of the serine/arginine-rich (SR) protein family, has been characterized as an important regulator of AS. However, the role of SRSF6 in regulating AS in prostate cancer remains unclear. In this study we analyzed SRSF6 expression levels in 550 prostate cancer tissue samples available in The Cancer Genome Atlas database and found that expression of SRSF6 was upregulated in all prostate cancer stages we examined. To investigate the biological consequences of SRSF6 overexpression, we constructed an SRSF6-overexpressing cell model and utilized RNA-seq to explore transcriptional changes. We also selected two groups of prostate cancer tumor samples in which SRSF6 was differentially expressed to analyze potential SRSF6-regulated AS. We hypothesized that overexpression of SRSF6 in cancer cells would induce large-scale changes in transcriptional expression levels and AS. We found that the pattern of SRSF6-regulated AS in cancer cells was similar to that observed in clinical samples and was enriched in pathways like DNA repair, double-strand break repair via homologous recombination and others. We also validated SRSF6-regulated AS events using RT-qPCR. Our findings highlighted how SRSF6 could regulate DNA repair-related pathways via regulation of AS to influence cancer progression in both cancer cells and prostate cancer tumor samples. These results greatly expand our current understanding of the mechanisms underlying SRSF6-mediated gene regulation and suggests the potential use of SRSF6 as a cancer therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138636 | GEO | 2020/10/20

REPOSITORIES: GEO

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