RNA methylation in hepatocellular carcinoma: from metabolic reprogramming and immune escape mechanisms to small molecule inhibitor development.

Abstract

Hepatocellular carcinoma (HCC) is a primary liver malignancy characterized by a high mortality rate and unfavorable prognosis. Altered epigenetic modifications have been closely associated with cancer development and tumor immune escape. RNA methylation is a pervasive epigenetic alteration. N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C), pseudouridine (Ψ), and 2'-O-methylation (Nm) are the main types of RNA methylation. Importantly, abnormal RNA modifications in HCC are key drivers in promoting the translation of oncogenic RNA transcripts. This not only provides cancer cells with a growth-promoting edge but also significantly contributes to tumorigenesis, fueling processes such as uncontrolled cell proliferation, invasion, and metastasis. RNA methylation influences metabolic reprogramming, immune cells, and immunological factors by modulating biological processes like RNA splicing, translation, stability, and translocation. Consequently, RNA methylation is pivotal in modulating biological processes including HCC tumor immunity, proliferation, invasion, and metastasis. This paper systematically examines the mechanisms and functions of these seven types of RNA methylations, offering a thorough overview of their roles and probable mechanisms within the HCC tumor microenvironment and immune system. We seek to offer novel insights and ways to enhance the effectiveness of HCC immunotherapy.