CSN1 facilitates proliferation and migration of hepatocellular carcinoma cells by upregulating cyclin A2 expression

Mol Med Rep. 2021 Jan;23(1):46. doi: 10.3892/mmr.2020.11684. Epub 2020 Nov 17.

Abstract

Constitutive photomorphogenesis 9 signalosome subunit 1 (CSN1) plays an important role in the ubiquitin-proteasome pathway and regulates various cellular processes, such as the cell cycle and DNA repair. The CSN complex consists of eight subunits (CSN1 to CSN8) and regulates the tumorigenesis of a variety of tumor types. However, the exact role of CSN1 in hepatocellular carcinoma (HCC) remains unclear. The present study evaluated the expression and biological effects of CSN1 in HCC tissue samples and cell lines. CSN1 was significantly overexpressed in HCC tissue and cell lines, compared with their normal counterparts. In patients with HCC, elevated CSN1 levels correlated with tumor size, tumor metastasis and tumor stage. Loss‑of‑function assays indicated that CSN1 knockdown inhibited the proliferation and migration HCC cells. In addition, CSN1 promoted the expression of cyclin A2 in a ubiquitination‑independent manner. Lastly, xenograft experiments indicated that CSN1 promoted HCC tumor growth <em>in vivo</em>. The present study suggested that CSN1 inhibition could represent a potential approach for the prevention of HCC progression and metastasis.

Keywords: CSN1; HCC; cyclin A2; cell proliferation.

MeSH terms

  • Adult
  • Animals
  • Apoptosis / genetics
  • COP9 Signalosome Complex / genetics*
  • COP9 Signalosome Complex / metabolism*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin A2 / genetics*
  • Cyclin A2 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • Transplantation, Heterologous
  • Up-Regulation

Substances

  • CCNA2 protein, human
  • Cyclin A2
  • COP9 Signalosome Complex