Research progress of circular RNAs and N6-methyladenosine modifications in the regulation of malignant tumors
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1.School of Clinical Medicine, Hebei University of Engineering, Handan, Hebei 056009, China;2.Department of Gastroenterology, 980th Hospital of PLA Joint Logistic Support Force, Shijiazhuang 050081, China;3.Xijing Hospital of Gastroenterology/State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, the Fourth Military Medical University, Xi'an 710032, China;4.Department of Anorectal Surgery, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China

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R730.2

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    Abstract:

    N6-methyladenosine (m6A) is the most common epigenetic modification in eukaryotic RNAs, which is dynamically balanced and reversibly changed in organisms through the coordinated regulation of methyltransferases, demethylases, and reader proteins. It affects the splicing, processing, localization, transportation, translation, and degradation of RNAs, thereby regulating the progression of tumors. Circular RNAs (circRNAs), as the novel multifunctional non-coding RNAs, possess characteristics like structural stability, evolutionary conservation, high abundance, and tissue specificity. Additionally, they participate in regulating various physiological and pathological activities by serving as a sponge of microRNAs (miRNAs), binding proteins, translating proteins, and modulating gene transcription and splicing, and are expected to provide new molecular markers and potential drug targets for the early diagnosis and treatment of tumors. Numerous studies have indicated that m6A and circRNAs can independently regulate oncogene expressions, and there is mutual regulatory interaction between them. M6A modification can regulate circRNA biogenesis, nuclear export, degradation, translation, and innate immunity. Similarly, circRNAs can regulate m6A modification through mechanisms such as acting as a miRNA sponge or binding m6A modification enzymes. Both participate in processes such as proliferation, migration, invasion, stemness, drug resistance, and the immune microenvironment of tumor cells, which will help discover more regulatory mechanisms and therapeutic targets for tumor research. However, given the complexity of m6A modification and circRNA biology, many aspects of research still need to be clarified. For example, m6A detection technology is not yet accurate, the database of m6A-modified circRNAs is still lacking, and efficient production methods and delivery system optimization for circRNAs are still in the early stages of development. Therefore, further in-depth research is needed on the interaction network between m6A modification and circRNAs. This article reviews the characteristics, formation mechanisms, and biological functions of circRNAs, along with an in-depth discussion on the basic concepts and current research status of m6A methylation modification, and also summarizes and analyzes the interaction between m6A modification and circRNAs and their impact on the occurrence and development of malignant tumors, as well as discusses their clinical application value and prospects, aiming to offer new perspectives for early tumor diagnosis, precision treatment, prognosis assessment, and drug development.

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WANG Yin'ge, LI Danxiu, ZHANG Wenyao, YANG Tao, JIN Haifeng. Research progress of circular RNAs and N6-methyladenosine modifications in the regulation of malignant tumors[J]. Chin J Gen Surg,2024,33(2):273-283.
DOI:10.7659/j. issn.1005-6947.2024.02.014

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History
  • Received:January 09,2024
  • Revised:February 18,2024
  • Adopted:
  • Online: March 09,2024
  • Published: