DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells

PLoS One. 2014 Feb 28;9(2):e89976. doi: 10.1371/journal.pone.0089976. eCollection 2014.

Abstract

Pre-mRNA processing factor 19 (Prp19) activates pre-mRNA spliceosome and also mediates DNA damage response. Prp19 overexpression in cells with functional p53 leads to decreased apoptosis and increases cell survival after DNA damage. Here we showed that in hepatocellular carcinoma (HCC) cells with inactive p53 or functional p53, Prp19 was down-regulated due to the impaired stability under chemotherapeutic drug treatment. Silencing Prp19 expression enhanced apoptosis of HCC cells with or without chemotherapeutic drug treatment. Furthermore high level of Prp19 may inhibit chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells through modulating myeloid leukemia cell differentiation 1 expression. These results indicated that targeting Prp19 may potentiate pro-apoptotic effect of chemotherapeutic agents on HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cycloheximide / pharmacology
  • DNA Damage
  • DNA Repair Enzymes / antagonists & inhibitors
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • DNA-Binding Proteins
  • Doxorubicin / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Humans
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Stability
  • Proteins / genetics
  • Proteins / metabolism
  • RNA Splicing Factors
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MLF1 protein, human
  • Nuclear Proteins
  • Proteins
  • RNA Splicing Factors
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Cycloheximide
  • DNA Repair Enzymes
  • PRPF19 protein, human
  • Cisplatin

Grant support

This study was partially supported by grants from Independent Study of Fudan University (NO. 20520133387, web: http://www.fudan.edu.cn/), Shanghai Science and Technology Commission (No. 10410709400 and 10411950100, web: http://www.stcsm.gov.cn/), China Postdoctoral Science Foundation (web: http://res.chinapostdoctor.org.cn/Program/Main.html) and National Nature Science Foundation of China (No. 81000968, No. 81101540, No. 81101637, and No. 81172273, web: http://www.nsfc.gov.cn/nsfc/cen/00/download.html), National Clinical Key Special Subject of China (web: http://www.moh.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.