Cyclin Y Modulates the Proliferation, Invasion, and Metastasis of Hepatocellular Carcinoma Cells

Med Sci Monit. 2018 Mar 20:24:1642-1653. doi: 10.12659/msm.906075.

Abstract

BACKGROUND Cyclin Y (CCNY) is a member of the cyclin family of proteins that regulate the cell cycle. The aims of this study were to compare the expression of CCNY in normal liver and human hepatocellular carcinoma (HCC), in normal and HCC cell lines, and in mouse HCC tumor xenografts. MATERIAL AND METHODS Tumor tissues from 55 patients diagnosed with HCC were studied for CCNY expression. Human HCC cell lines, SK-Hep1, HepG2, HEP3B, HuH7 and L02 were studied using the MTT cell proliferation assay, cell apoptosis, transwell and wound healing assays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to measure CCNY expression. Indirect immunofluorescence was used to assess cell apoptosis. In vivo xenograft mouse model was constructed and examined histologically. RESULTS Expression of CCNY in human HCC tumor tissues was significantly increased when compared with adjacent normal liver (all P<0.05). HCC cells grown in vitro showed significantly increased expression of CCNY, cell proliferation, and migration, and a reduced rate of apoptosis, compared with cells with CCNY knockdown (siRNA) (all P<0.05). In the xenograft mouse model, tumor volume and weight in the CCNY overexpression group were significantly increased, compared with CCNY knockdown (siRNA) group (all P<0.05). CONCLUSIONS In tissue samples of human HCC, and human HCC cell lines, increased expression of CCNY was significantly associated with cell proliferation and migration. Further studies are recommended to evaluate the role of CCNY as a potential diagnostic biomarker or target for treatment in human HCC.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transfection
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays

Substances

  • CCNY protein, human
  • Cyclins
  • RNA, Messenger