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A-to-I RNA editing shows dramatic up-regulation in osteosarcoma and broadly regulates tumor-related genes by altering

Fuqun Ge1, Xinyue Cao2, Yankai Jiang3

  • 1Department of Joint Surgery, The Second Hospital of Shandong University, Jinan, 250033, Shandong, China.

Journal of Applied Genetics
|August 5, 2023
PubMed

Insights

RNA editing efficiency significantly increases in osteosarcoma, driven by elevated ADAR1/ADAR2 enzymes. This dysregulation impacts microRNA binding sites, potentially driving oncogenesis and offering new diagnostic avenues for this bone cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • A-to-I RNA editing is a crucial post-transcriptional modification in animals.
  • Dysregulation of RNA editing is implicated in various human cancers.
  • The role of RNA editing in osteosarcoma remains unexplored.

Purpose of the Study:

  • To investigate the role and impact of RNA editing in osteosarcoma.
  • To identify differential RNA editing sites (DES) between osteosarcoma and normal tissues.
  • To explore the functional consequences of altered RNA editing in osteosarcoma oncogenesis.

Main Methods:

  • Analysis of RNA-sequencing data from 24 primary osteosarcoma patients and 3 healthy controls.
  • Systematic profiling of RNA editomes to identify differential editing sites (DES).
  • Quantitative analysis of RNA editing efficiency and enzyme expression (ADAR1, ADAR2).

Main Results:

  • Osteosarcoma exhibits dramatically increased RNA editing efficiency.
  • Significant upregulation of ADAR1 and ADAR2 enzymes observed in osteosarcoma.
  • Differential editing sites (DES) are enriched in 3'UTRs, particularly in microRNA binding regions of oncogenes like EMP2.
  • Upregulated DES abolish microRNA suppression, leading to elevated expression of tumor-promoting genes.

Conclusions:

  • RNA editing plays a significant role in osteosarcoma development.
  • An RNA editing-dependent pathway may contribute to osteosarcoma oncogenesis.
  • Findings provide valuable molecular insights for potential osteosarcoma prognosis and diagnosis.
Keywords:
3’UTRA-to-I RNA editingDifferentialOncogenesOsteosarcomamiRNA target

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