ADAR2 Regulates Malignant Behaviour of Mesothelioma Cells Independent of RNA-editing Activity

Anticancer Res. 2020 Mar;40(3):1307-1314. doi: 10.21873/anticanres.14072.

Abstract

Background/aim: Malignant pleural mesothelioma (MPM) is an intractable cancer, and causes of its malignant transformation are not well known. Adenosine deaminase acting on RNA (ADAR) is an RNA-editing enzyme that converts adenosine into inosine in double-stranded RNAs potentially involved in malignant development.

Materials and methods: To examine the role of ADAR1 and ADAR2 in MPM, small interfering RNAs (siRNAs) against ADAR1 or ADAR2 were used.

Results: Transfection of siRNA against ADAR2 suppressed proliferation, motility, and invasiveness of MPM cells expressing both ADAR1 and ADAR2; however, siRNA against ADAR1 did not affect these cellular activities. Overexpression of ADAR2, that was incapable of binding to RNA, suppressed growth, motility, and invasion of MPM cells. However, overexpression of ADAR2 that had no enzyme activity did not alter the malignant properties of MPM cells.

Conclusion: Enhancement of the malignant characteristics of cultured MPM cells via ADAR2 was independent of RNA-editing activity.

Keywords: A-to-I RNA editing; ADAR; mesothelioma cells.

MeSH terms

  • Adenosine Deaminase / biosynthesis
  • Adenosine Deaminase / genetics
  • Adenosine Deaminase / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mesothelioma / enzymology
  • Mesothelioma / genetics*
  • Mesothelioma / metabolism*
  • Mesothelioma / pathology
  • Mesothelioma, Malignant
  • RNA Editing*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transfection

Substances

  • RNA, Small Interfering
  • RNA-Binding Proteins
  • ADARB1 protein, human
  • Adenosine Deaminase