N⁶-methyladenosine (m⁶A) modification in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the deadliest cancers of human, the tumor-related death of which ranks third among the common malignances. N⁶-methyladenosine (m⁶A) methylation, the most abundant internal modification of RNA in mammals, participates in the metabolism of mRNA and interrelates with ncRNAs. In this paper, we overviewed the complex function of m⁶A regulators in HCC, including regulating the tumorigenesis, progression, prognosis, stemness, metabolic reprogramming, autophagy, ferroptosis, drug resistance and tumor immune microenvironment (TIME). Furthermore, we elucidated the interplay between m⁶A modification and non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Finally, we summarized the potential of m⁶A regulators as diagnostic biomarkers. What's more, we reviewed the inhibitors targeting m⁶A enzymes as promising therapeutic targets of HCC. We aimed to help understand the function of m⁶A methylation in HCC systematically and comprehensively so that more effective strategies for HCC treatment will be developed.