EIF4G2 Promotes HCC Progression

Aberrant translation from mRNAs to proteins plays a crucial role in the pathogenesis of various cancers. Here, we revealed that the key proteins involved in translation were up-regulated in two hepatocellular carcinoma (HCC) cohorts. Specifically, we identified the translation initiation factor EIF4G2 as a marker of poor prognosis, linked to unfavorable overall survival (OS) outcomes. Our in vitro and in vivo studies confirmed that EIF4G2 promotes the development and metastasis of HCC. As an essential translation initiation factor, EIF4G2 knockdown disrupts polyribosome stability and inhibits nascent protein synthesis in the Huh-7 and MHCC97H cell lines. By com-paring the proteome and transcriptome of Huh-7 cells, we further identified PLEKHA1 as an essential target of EIF4G2 with IRES-dependent translation. PLEKHA1 was able to rescue the inhibitory effects of EIF4G2 knockdown on cell migration and invasion in both Huh-7 and MHCC97H cells. This research provides novel insights into the critical role of EIF4G2-dependent translation in cancer, where PLEKHA1 promotes HCC progression.