Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma

Aging (Albany NY). 2020 Feb 11;12(3):3025-3041. doi: 10.18632/aging.102797. Epub 2020 Feb 11.

Abstract

Background: Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers. However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear.

Results: High expression of OLA1 in HCC was detected in public datasets and clinical samples, and correlated with poor prognosis. Downregulation of OLA1 significantly inhibited the proliferation, migration, invasion and tumorigenicity of HCC cells. Mechanistically, GSEA showed that OLA1 might promote tumor progression by regulating the cell cycle and apoptosis. In addition, OLA1 knockdown resulted in G0/G1 phase arrest and high levels of apoptosis. OLA1 could bind with P21 and upregulate CDK2 expression to promote HCC progression.

Conclusions: Overall, these findings uncover a role for OLA1 in regulating the proliferation and apoptosis of HCC cells.

Materials and methods: The Cancer Genome Atlas and Gene Expression Omnibus datasets were analyzed to identify gene expression. Immunohistochemistry staining, western blot and real-time polymerase chain reaction were performed to evaluate OLA1 expression in samples. Cell count Kit-8, wound-healing, transwell and flow cytometry assays were used to analyze HCC cell progression. Subcutaneous xenotransplantation models were used to investigate the role of OLA1 in vivo. Coimmunoprecipitation was used to analyze protein interactions.

Keywords: CDK2; HCC; OAL1; prognosis; tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / metabolism*
  • Male
  • Mice
  • Mice, Nude

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Adenosine Triphosphatases
  • GTP-Binding Proteins
  • OLA1 protein, human