Large-scale omics data reveal the cooperation of mutation-circRNA-miRNA-target gene network in liver cancer oncogenesis

Future Oncol. 2022 Jan;18(2):163-178. doi: 10.2217/fon-2021-0940. Epub 2021 Oct 22.

Abstract

Aims: Clarifying the initial trigger of the differentially expressed genes in cancers helps researchers understand the cellular system as a whole network. Materials & methods: We retrieve the transcriptome and translatome of tumor and normal tissues from ten liver cancer patients and define differentially expressed genes and tumor-specific mutations. We associate the oncogenesis with the mutations by target prediction and experimental verification. Results: Upregulated genes have tumor-specific mutations in 3'UTRs that abolish the binding of miRNAs. For downregulated genes, their corresponding miRNAs are mutually targeted by two circRNAs, with mutations in base-pairing regions. Transfection experiments support the oncogenic role of these mutations. Conclusions: The tumor-specific mutations serve as the initial trigger of liver cancer. The mutation-circRNA-miRNA-target gene chain is completed.

Keywords: circRNA; differentially expressed genes; liver cancer; miRNA; mutation.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carcinogenesis / genetics*
  • Computational Biology
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Humans
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutation
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Seq
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger