Multiomics analysis identifies key genes and pathways related to N6-methyladenosine RNA modification in ovarian cancer

Epigenomics. 2021 Sep;13(17):1359-1383. doi: 10.2217/epi-2021-0204. Epub 2021 Sep 22.

Abstract

Aims: To explore the pathways and target genes related to N6-methyladenosine (m6A) methylation in ovarian cancer and their effect on patient prognosis. Methods & materials: The Cancer Genome Atlas was used to screen genes related to m6A regulators in terms of gene expression, mutation and copy number variation. These genes were subjected to pathway enrichment analysis. Prognosis-related genes were screened and involved in risk signature construction. Immunohistochemistry was used for verification. Results: We obtained 1408 genes dysregulated in parallel to m6A regulators, which were mainly involved in the platelet activation pathway. The m6A-related signature was constructed based on the expression of four prognosis-related genes (RPS6KA2, JUNB, HNF4A and P2RX1). Conclusion: This work provides new insights into the mechanism of m6A methylation in ovarian cancer.

Keywords: RPS6KA2; bioinformatics; m6A RNA methylation; ovarian cancer; platelet activation; risk signature.

Plain language summary

Lay abstract N6-methyladenosine (m6A) methylation is the most common type of modification on mRNA. m6A methylation can affect the biological function of cells by affecting the protein expression level of mRNA. The process of m6A modification is controlled by many m6A regulators, which are dysregulated in ovarian cancer. Our research aims to screen the genes that are related to m6A regulation to analyze targets and mechanisms in ovarian cancer. We screened 1408 m6A-related genes, which are mainly involved in the platelet activation pathway. Among them, RPS6KA2 and JUNB were significantly related to poor prognosis of patients with ovarian cancer. RPS6KA2 was positively correlated with the m6A regulator METTL3 in ovarian cancer. Our study provides a basis for future mechanism studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / genetics
  • Computational Biology
  • DNA Copy Number Variations*
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Middle Aged
  • Mutation
  • Ovarian Neoplasms / genetics*
  • Platelet Activation
  • RNA Processing, Post-Transcriptional / genetics*
  • Ribosomal Protein S6 Kinases, 90-kDa / genetics
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*

Substances

  • N-methyladenosine
  • Methyltransferases
  • METTL3 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3
  • Adenosine