The role of splicing factor PRPF8 in breast cancer

Technol Health Care. 2022;30(S1):293-301. doi: 10.3233/THC-THC228028.

Abstract

Background: Alternative splicing is a mechanism to produce different proteins with diverse functions from one gene. Many splicing factors play an important role in cancer progression. PRPF8 is a core protein component of the spliceosome complex, U4/U6-U5 tri-snRNP.

Objective: However, PRPF8 involved in mRNA alternative splicing are rarely included in the prognosis.

Methods: We found that PRPF8 was expressed in all examined cancer types. Further analyses found that PRPF8 expression was significantly different between the breast cancer and paracancerous tissues.

Results: Survival analyses showed that PRPF8-high patients had a poor prognosis, and the expression of PRPF8 is associated with distant metastasis-free survival (DMFS) and post progression survival (PPS). Gene Set Enrichment Analysis (GSEA) has revealed that PRPF8 expression is correlated with TGF-β, JAK-STAT, and cell cycle control pathways. Consistent with these results, upon PRPF8 silencing, the growth of MCF-7 cells was reduced, the ability of cell clone formation was weakened, and p⁢21 expression was increased.

Conclusions: These results have revealed that PRPF8 is a significant factor for splicing in breast cancer progression.

Keywords: PRPF8; alternative splicing; breast cancer; prognosis.

MeSH terms

  • Breast Neoplasms* / genetics
  • Female
  • HeLa Cells
  • Humans
  • RNA Splicing Factors / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoprotein, U4-U6 Small Nuclear / genetics
  • Ribonucleoprotein, U4-U6 Small Nuclear / metabolism
  • Ribonucleoprotein, U5 Small Nuclear* / genetics
  • Ribonucleoprotein, U5 Small Nuclear* / metabolism

Substances

  • PRPF8 protein, human
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Ribonucleoprotein, U5 Small Nuclear