Lymphoid-specific helicase promotes the growth and invasion of hepatocellular carcinoma by transcriptional regulation of centromere protein F expression

Cancer Sci. 2019 Jul;110(7):2133-2144. doi: 10.1111/cas.14037. Epub 2019 May 25.

Abstract

Lymphoid-specific helicase (LSH) is overexpressed in tumor tissues and its overexpression is associated with poor prognosis in several cancers. However, the role and molecular mechanism of LSH in hepatocellular carcinoma (HCC) remains largely unknown. Herein, we report that LSH was overexpressed in tumor tissues of HCC, and overexpression of LSH was associated with poor prognosis from a public HCC database, and validated by clinical samples from our department. Ectopic LSH expression promoted the growth of HCC cells in vivo and in vitro. Mechanistically, LSH overexpression promoted tumor growth by activating transcription of centromere protein F (CENPF). Clinically, overexpression of LSH and/or CENPF correlated with shorter overall survival and higher cumulative recurrence rates of HCC. In conclusion, LSH promotes tumor growth of HCC through transcriptional regulation of CENPF expression. Therefore, LSH may be a novel predictor for prognosis and a potential therapeutic target for HCC.

Keywords: CENPF; ChIP-seq; HCC; LSH; RNA-seq.

MeSH terms

  • Aged
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA Helicases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Prognosis
  • Sequence Analysis, RNA
  • Survival Analysis
  • Tissue Array Analysis
  • Transcriptional Activation
  • Up-Regulation*

Substances

  • Chromosomal Proteins, Non-Histone
  • Microfilament Proteins
  • centromere protein F
  • DNA Helicases
  • HELLS protein, human