Skip to main navigation menu Skip to main content Skip to site footer

Function and Molecular Mechanism of m5C participating Malignant Tumors

Abstract

5-methylcytosine (m5C) plays a crucial role in gene expression regulation and RNA metabolism, and it is an important form of RNA epigenetic modification. This article systematically summarizes the molecular mechanisms of m5C regulation, including its dynamic regulatory network composed of methyltransferases, demethylases, and recognition proteins, and explores the function and mechanism of m5C in RNA stability, translation, and nucleocytoplasmic transport. m5C participates in the development of tumors by regulating oncogene expression, immune microenvironment remodeling, and metabolic reprogramming. The correlation between m5C modification levels and tumor patient prognosis is analyzed, and the potential value of m5C as a tumor diagnostic biomarker and therapeutic target is explored. High throughput sequencing and computational biology have driven m5C investigation, but the development and innovation of detection technologies, mechanisms for regulating tissue heterogeneity, and synergistic effects with other modifications such as m6A remain current challenges. In future, it needs to further be analyzed the precise regulatory network of m5C, providing theoretical basis for developing targeted intervention strategies to promote its application in precision medicine.

Keywords

5-methylcytosine (m5C), Epigenetic modification, RNA, Tumorigenesis, Post transcriptional, Immune microenvironment

PDF

References

  1. Chen Y S, Yang W L, Zhao Y L, et al. Dynamic transcriptomic m5 C and its regulatory role in RNA processing. Wiley interdisciplinary reviews. RNA, 2021, 12(4): e1639.
  2. Gao Y, Fang J. RNA 5-methylcytosine modification and its emerging role as an epitranscriptomic mark. RNA Biology, 18(Suppl 1): 117-127.
  3. Squires J E, Patel H R, Nousch M, et al. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Research, 2012, 40(11): 5023-5033.
  4. Gama-Sosa M A, Slagel V A, Trewyn R W, et al. The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Research, 1983, 11(19): 6883-6894.
  5. Liu J, Huang T, Zhang Y, et al. Sequence- and structure-selective mRNA m5C methylation by NSUN6 in animals. National Science Review, 2020, 8(6): nwaa273.
  6. Kuznetsov N A, Kanazhevskaya L Yu, Fedorova O S. DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases. International Journal of Molecular Sciences, 2021, 22(19): 10540.
  7. Ding Y, Bajpai A K, Wu F, et al. 5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia. Aging (Albany NY), 2024, 16(3): 2340.
  8. Chen C, Chen L Y, Zhang J X, et al. 5-Methylcytosine (m5C) Modification Patterns and Tumor Immune Infiltration Characteristics in Clear Cell Renal Cell Carcinoma. Current Oncology, 2022, 30(1): 559-574.
  9. He Y, Yu X, Li J, et al. Role of m5C-related regulatory genes in the diagnosis and prognosis of hepatocellular carcinoma. American Journal of Translational Research, 2020, 12(3): 912-922.
  10. Lu Y, Du W, Yu D. m5C Methylation modification and its research progress in tumor immunotherapy. Prevention and Treatment of Oral Diseases, 2024,32(02):143-148.
  11. Gu X, Ma X, Chen C, et al. Vital roles of m5C RNA modification in cancer and immune cell biology. Frontiers in Immunology, 2023, 14: 1207371.
  12. Qiu L, Jing Q, Li Y, et al. RNA modification: mechanisms and therapeutic targets. Molecular Biomedicine, 2023, 4: 25.
  13. Cui L, Ma R, Cai J, et al. RNA modifications: importance in immune cell biology and related diseases. Signal Transduction and Targeted Therapy, 2022, 7: 334.
  14. Zhou J, Zhao D, Li J, et al. Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing. eLife, 13: RP98166.
  15. Xue C, Zhao Y, Li L. Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer. Biomarker Research, 2020, 8: 43.
  16. Li M, Tao Z, Zhao Y, et al. 5-methylcytosine RNA methyltransferases and their potential roles in cancer. Journal of Translational Medicine, 2022, 20: 214.
  17. Zhang X, An K, Ge X, et al. NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation. Breast Cancer Research : BCR, 2024, 26: 94.
  18. Wei Z, Panneerdoss S, Timilsina S, et al. Topological Characterization of Human and Mouse m5C Epitranscriptome Revealed by Bisulfite Sequencing. International Journal of Genomics, 2018, 2018: 1351964.
  19. He Y, Yu X, Zhang M, et al. Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers. World Journal of Surgical Oncology, 2021, 19: 224.
  20. Liu H. Study on the specificity of neuronal RNA m6A and m5C methylation modification[D]. Wuhan University of Science and Technology,v2022.
  21. Huan M. The impact of RNA m5C methylation regulated genes on the progression and clinical prognosis of cutaneous melanoma[D].Zhengzhou University,2022.
  22. Chen B, Xi Y, Zhao J, et al. m5C regulator-mediated modification patterns and tumor microenvironment infiltration characterization in colorectal cancer: One step closer to precision medicine. Frontiers in Immunology, 2022, 13: 1049435.
  23. Lai Z, Liang G, Luo M. m5CThe role of modifying regulatory factors in pan cancer and analysis of potential inhibitors. Lingnan Modern Clinical Surgery,2023,23(01):64-70.
  24. Yun D, Yang Z, Zhang S, et al. An m5C methylation regulator-associated signature predicts prognosis and therapy response in pancreatic cancer. Frontiers in Cell and Developmental Biology, 2022, 10: 975684.
  25. Anwar Jumel Abdullah, Burland Yerkenbek, Sun Lili, et al. Prognostic prediction model and drug sensitivity analysis of triple negative breast cancer based on m5C related genes. Advances in biotechnology, 2024,14(01):149-159.