The roles of N6-methyladenosine and its target regulatory noncoding RNAs in tumors: classification, mechanisms, and potential therapeutic implications

作者：Liu, Ziying; Gao, Lei; Cheng, Long; Lv, Gaoyuan; Sun, Bei; Wang, Gang^*; Tang, Qiushi^*

来源：Experimental and Molecular Medicine, 2023, 55(3): 487-501.

DOI：10.1038/s12276-023-00944-y

• RESOLUTION MAPPING REVEALS
• MESSENGER-RNA
• HEPATOCELLULAR-CARCINOMA
• M6A MODIFICATION
• N-6-METHYLADENOSINE RNA
• PROMOTES METASTASIS
• LUNG ADENOCARCINOMA
• FOXD2-AS1 PROMOTES
• CANCER PROGRESSION
• CELL-PROLIFERATION

N6-methyladenosine (m6A) is one of the epigenetic modifications of RNA. The addition of this chemical mark to RNA molecules regulates gene expression by affecting the fate of the RNA molecules. This posttranscriptional RNA modification is reversible and regulated by methyltransferase "writers" and demethylase "erasers". The fate of m6A-modified RNAs depends on the function of different "readers" that recognize and bind to them. Research on m6A methylation modification has recently increased due to its important role in regulating cancer progression. Noncoding RNAs (ncRNAs) are a class of RNA molecules that are transcribed from the genome but whose roles have been overlooked due to their lack of well-defined potential for translation into proteins or peptides. However, this misconception has now been completely overturned. ncRNAs regulate various diseases, especially tumors, and it has been confirmed that they play either tumor-promoting or tumor-suppressing roles in almost all types of tumors. In this review, we discuss the m6A modification of different types of ncRNA and summarize the mechanisms involved. Finally, we discuss the progress of research on clinical treatment and discuss the important significance of the m6A modification of ncRNAs in the clinical treatment of tumors. @@@ Non-coding RNAs: Modification by adding methyl groupsThe reversible addition of a chemical methyl group (CH3) to the base adenine in RNA molecules, creating N6-methyladenosine, regulates the activity of many non-coding RNAs that, unlike messenger RNAs, do not code for the formation of proteins. These RNAs can regulate gene activity. Researchers in China led by Gang Wang at Harbin Medical University, and Qiushi Tang at the Chinese Medical University, Liaoning, review the molecular mechanisms and significance of 'm6A modification' of non-coding RNAs. They focus on the progress of research into the role of m6A modification in cancer and its potential relevance for diagnosis and treatment. Approaches to treating cancer by interfering with m6A modification have been explored in mice. Future research will aim to translate the promise of these early animal studies into tests in human cells and clinical trials in patients.

• 单位
  中国医科大学; 1; 哈尔滨医科大学