Houston Methodist

ABSTRACT Primary liver cancer remains a significant global public health challenge, characterized by persistently high incidence and mortality. This review synthesizes current epidemiological data to analyze trends and etiological shifts, with particular emphasis on China, which bears over 40% of the global burden. Findings highlight a transition in dominant risk factors from viral hepatitis to metabolic dysfunction‐associated steatotic liver disease (MASLD), alongside persistent threats from aflatoxin exposure and lifestyle behaviors. Evidence‐based prevention strategies, including universal hepatitis B virus (HBV) vaccination, antiviral therapy expansion, aflatoxin control, and early metabolic intervention, are critical to reducing disease burden. The integration of artificial intelligence into screening and management represents a promising advancement. A multi‐faceted approach combining vaccination, surveillance, lifestyle modification, and technological innovation is essential for effective global liver cancer control.

Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a widespread modification in metazoans. Cumulative evidence has revealed the altered A-to-I editing profiles in cancers, but the underlying mechanism remains unclear. Here, we discover the well-known histone lysine methyltransferase enhancer of zeste homologue 2 (EZH2) as an unexplored ADAR interactor and editing regulator in prostate cancer (PCa). Through competing with interleukin enhancer binding factor 2 (ILF2) for ADAR1 binding, EZH2 reshapes the substrate selectivity of ADAR1 and thus exhibits a bidirectional role in editing regulation. Moreover, EZH2 depletion induces the translational repression of transportin-1 (TRN1), which further results in the accumulation of cytoplasmic ADAR1p110 isoform to protect many oncogenic transcripts from degradation. Consistently, depletion of ADAR1 dramatically enhances the sensitivity of cancer cells and tumors to EZH2 selective degraders. Collectively, our study sheds new light on a link between two layers of epigenetic regulations at histone modification and RNA editing levels, demonstrates a previously uncharacterized role of EZH2 in RNA editing and mRNA stability independently of its lysine methyltransferase activity, and reveals the significance of EZH2-ADAR1 cascade in governing RNA editing and mRNA stability, which may provide additional perspectives for the advancement of EZH2-targeting cancer therapies.