CPSF7 regulates liver cancer growth and metastasis by facilitating WWP2-FL and targeting the WWP2/PTEN/AKT signaling pathway

Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118624. doi: 10.1016/j.bbamcr.2019.118624. Epub 2019 Dec 12.

Abstract

Alternative splicing within a gene can create different versions of an mRNA, called isoforms. CFIm, composed of a small subunit CFIm25 and two large subunits CFIm68 and CFIm59 (also known as CPSF7), has been proposed as an enhancer-dependent activator of mRNA 3' processing. In this study, we investigated the role of CPSF7 in hepatocellular carcinoma. Experimental evidence suggests that the expression level of CPSF7 is higher in liver cancer cells and tissues than in non-tumor hepatic cells and tissues. Furthermore, knockdown of CPSF7 effectively suppressed cell proliferation, migration and colony formation in liver cancer cells by inhibiting PTEN/AKT signaling. CPSF7 promoted WWP2-FL due to the presence of PTEN ubiquitination sites in this longer transcript. Taken together, we identified that CPSF7 regulates liver cancer growth by targeting WWP2-FL that in turn regulates AKT activation in a PTEN-dependent manner.

Keywords: Alternative polyadenylation; CPSF7; Hepatocellular carcinoma; PTEN/AKT signaling; WWP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • PTEN Phosphohydrolase / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • RNA Recognition Motif Proteins / genetics
  • RNA Recognition Motif Proteins / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transplantation, Heterologous
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • mRNA Cleavage and Polyadenylation Factors / antagonists & inhibitors
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • CPSF7 protein, human
  • Protein Isoforms
  • RNA Recognition Motif Proteins
  • RNA, Small Interfering
  • mRNA Cleavage and Polyadenylation Factors
  • WWP2 protein, human
  • Ubiquitin-Protein Ligases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human