EIF4G2 Promotes\nHepatocellular Carcinoma Progression\nvia IRES-dependent PLEKHA1 Translation Regulation

Hepatocellular\ncarcinoma (HCC) is a highly lethal cancer,\nand proteomic\nstudies have shown increased protein diversity and abundance in HCC\ntissues, whereas the role of protein translation has not been extensively\nexplored in HCC. Our research focused on key molecules in the translation\nprocess to identify a potential contributor in HCC. We discovered\nthat EIF4G2, a crucial translation initiation factor, is significantly\nupregulated in HCC tissues and associated with poor prognosis. This\nstudy uniquely highlights the impact of EIF4G2 deletion, which suppresses\ntumor growth and metastasis both in <i>vitro</i> and in <i>vivo</i>. Furthermore, polysome analysis and nascent protein\nsynthesis assays revealed EIF4G2’s role in regulating protein\ntranslation, specifically identifying PLEKHA1 as a key translational\nproduct. This represents a novel mechanistic insight into HCC malignancy.\nRNA immunoprecipitation (RIP) and Dual-luciferase reporter assays\nfurther revealed that EIF4G2 facilitates PLEKHA1 translation via an\nIRES-dependent manner. Importantly, the synergistic effects of EIF4G2\ndepletion and PLEKHA1 reduction in inhibiting cell migration and invasion\nunderscore the therapeutic potential of targeting this axis. This\nstudy not only advances our understanding of translational regulation\nin HCC but also identifies the EIF4G2-PLEKHA1 axis as a promising\ntherapeutic target, offering new avenues for intervention in HCC treatment.