Over 170 chemical modifications have been identified in protein-coding and noncoding RNAs and shown to exhibit broad impacts on gene expression. Dysregulation of RNA modifications caused by aberrant expression of or mutations in RNA modifiers aberrantly reprograms the epitranscriptome and skews global gene expression, which in turn leads to tumorigenesis and drug resistance. Here we review current knowledge of the functions and underlying mechanisms of aberrant RNA modifications in human cancers, particularly several common RNA modifications, including N⁶-methyladenosine (m⁶A), A-to-I editing, pseudouridine (ψ), 5-methylcytosine (m⁵C), 5-hydroxymethylcytosine (hm⁵C), N¹-methyladenosine (m¹A), and N⁴-acetylcytidine (ac4C), providing insights into therapeutic implications of targeting RNA modifications and the associated machineries for cancer therapy.

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