RNA‐Binding Protein DHX9 Enhances Radioresistance in Metastatic Hepatocellular Carcinoma by Activation of the PI3K/Akt Pathway Through Enhanced EEF1A2 mRNA Stability

ABSTRACT This study elucidated the role of Eukaryotic Elongation Factor 1 Alpha 2 (EEF1A2) and RNA‐binding protein DExH‐Box helicase 9 (DHX9) in hepatocellular carcinoma (HCC) radioresistance and molecular mechanisms. HCC tissues were compared with adjacent normal liver tissues by bioinformatics analysis. Clinical samples were evaluated according to RECIST 1.1 criteria. Regulatory interactions between EEF1A2 and DHX9 were analyzed. The effect of targeting these genes on HCC radioresistance was assessed. EEF1A2 was significantly elevated in radiation‐resistant HCC tissues and cell lines. EEF1A2 overexpression was associated with enhanced cellular proliferation, reduced apoptosis, increased metastatic potential. Decreasing EEF1A2 significantly improved radiosensitivity. DHX9 stabilized EEF1A2 mRNA and increased EEF1A2 expression. Inhibition of DHX9 produced similar radiosensitizing effects as those observed with EEF1A2 knockdown. The interaction between DHX9 and EEF1A2 activated the PI3K/Akt pathway. The DHX9/EEF1A2 axis plays a pivotal role in the radioresistance of HCC by modulating the PI3K/Akt pathway.