Decreased expression of ARID1A invasively downregulates the expression of ribosomal proteins in hepatocellular carcinoma

Biomark Med. 2021 May;15(7):497-508. doi: 10.2217/bmm-2020-0464. Epub 2021 Mar 26.

Abstract

Background: There was increasing evidence showing that ARID1A alterations correlated with higher tumor mutational burden, but there were limited studies focusing on the adaptive mechanisms for tumor cells to survive under excessive genomic alterations. Materials & methods: To further explore the adaptive mechanisms under ARID1A alterations, we performed RNA sequencing in ARID1A knockdown hepatocellular carcinoma cell lines, and demonstrated that decreased expression of ARID1A controlled global ribosomal proteins synthesis. The results were further confirmed by quantitative reverse transcription-PCR and bioinformatic analysis in The Cancer Genome Atlas Liver Hepatocellular Carcinoma database. Conclusion: The present study was the first to demonstrate that ARID1A might be involved in the translation pathway and served as an adaptive mechanism for tumor cells to survive under stress.

Keywords: ARID1A; HCC; ribosomal proteins; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Databases, Genetic
  • Down-Regulation
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mutation
  • Neoplasm Staging
  • Ribosomal Proteins / antagonists & inhibitors*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Survival Rate
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ARID1A protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ribosomal Proteins
  • Transcription Factors