Prp19 Arrests Cell Cycle via Cdc5L in Hepatocellular Carcinoma Cells

Int J Mol Sci. 2017 Apr 7;18(4):778. doi: 10.3390/ijms18040778.

Abstract

Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. Recently, it has been identified as a candidate oncogene in hepatocellular carcinoma (HCC). However, the role of Prp19 in tumor biology is still elusive. Here, we reported that Prp19 arrested cell cycle in HCC cells via regulating G2/M transition. Mechanistic insights revealed that silencing Prp19 inhibited the expression of cell division cycle 5-like (Cdc5L) via repressing the translation of Cdc5L mRNA and facilitating lysosome-mediated degradation of Cdc5L in HCC cells. Furthermore, we found that silencing Prp19 induced cell cycle arrest could be partially resumed by overexpressing Cdc5L. This work implied that Prp19 participated in mitotic progression and thus could be a promising therapeutic target of HCC.

Keywords: cell cycle; cell division cycle 5-like; lysosome-mediated degradation; pre-mRNA processing factor 19; repressing the translation of mRNA; translation.

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Cycle
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Lysosomes / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • CDC5L protein, human
  • Cell Cycle Proteins
  • Nuclear Proteins
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • DNA Repair Enzymes
  • PRPF19 protein, human