Biological functions and molecular mechanisms of exosome-derived circular RNAs and their clinical implications in digestive malignancies: the vintage in the bottle

Ann Med. 2024 Dec;56(1):2420861. doi: 10.1080/07853890.2024.2420861. Epub 2024 Nov 1.

Abstract

Background: Circular RNAs (circRNAs) are identified as a novel family of endogenous RNA molecules through 'back-splicing' and covalently linked at the 5' and 3' ends. Emerging researches have demonstrated circRNAs are stable and abundant in exosomes called exosomal circRNAs (exo-circRNA).

Materials and methods: We searched recent studies and references to summary the research progress of exosomal circRNA.

Results: Recent studies have revealed that exosome-derived circRNAs including exo-CDR1as, exo-circRanGAP1, exo-circIAR play vital roles in cell proliferation and apoptosis, epithelial mesenchymal transition, invasion and metastasis, angiogenesis, immune evasion, cellular crosstalk, cancer cachexia through a variety of biological mechanisms, such as serving as microRNA sponges, interacting with RNA binding proteins, regulating gene transcription, N6-Methyladenosine modification and so on. Due to their characteristics of origin, structure, properties and biological functions, exo-circRNAs are expected to apply in precious diagnosis and prognostic indicators, improving drug and radiation resistance and sensitivity, becoming biological therapeutic targets.

Conclusion: We summarize the update of digestive malignancies associated exo-circRNAs in biogenesis, biological functions, molecular mechanisms, clinical implications, potential applications and experimental technique in order to effectively promote transformation and application in the future.

Keywords: Exosomal circRNA; biological function; clinical implication; digestive malignancies; exosomes; molecular mechanism.

Publication types

  • Review

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Proliferation / genetics
  • Digestive System Neoplasms / genetics
  • Digestive System Neoplasms / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neovascularization, Pathologic / genetics
  • RNA / genetics
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism

Substances

  • RNA, Circular
  • Biomarkers, Tumor
  • RNA
  • MicroRNAs

Grants and funding

This study was supported by grants from the Key Scientific and Technological Projects of Ningbo (No. 2021Z133), Ningbo Top Medical and Health Research Program (No. 2023020612), National Natural Science Foundation of China (No. 81702367), the Medical and Health Research Project of Zhejiang Province (No. 2024KY1515), and the Youth Medical Backbone Talents Training Program of Ningbo.