Large-scale Omics Data Reveal the Cooperation of Mutation-circRNA-miRNA-Target Gene Network in Liver Cancer Oncogenesis

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

Author contributions

S. Chang, J. Li, Q. Li, L. Xie, and C. Yu: Methodology, writing of original draft. S. Wang: Conceptualization, supervision, writing of original draft, review and editing. All authors approved the submission of this article.

Acknowledgments

We thank colleagues who gave precious suggestions to this study.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.