EIF4G2 Promotes Hepatocellular Carcinoma Progression via IRES-dependent PLEKHA1 Translation Regulation.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Hepatocellular carcinoma (HCC) is a lethal malignancy with poorly understood translational regulation mechanisms.
• Proteomic studies indicate altered protein expression in HCC, but the role of protein translation remains underexplored.

Purpose of the Study:

• To investigate the role of key translation initiation factors in HCC.
• To identify novel molecular targets for HCC therapy.

Main Methods:

• Analysis of EIF4G2 expression in HCC tissues.
• In vitro and in vivo studies of EIF4G2 deletion effects on tumor growth and metastasis.
• Polysome profiling, nascent protein synthesis assays, RNA immunoprecipitation (RIP), and Dual-luciferase reporter assays.

Main Results:

• EIF4G2 is significantly upregulated in HCC and correlates with poor prognosis.
• EIF4G2 deletion suppresses HCC tumor growth and metastasis.
• EIF4G2 enhances PLEKHA1 translation via an IRES-dependent mechanism, promoting HCC malignancy.
• Combined EIF4G2 and PLEKHA1 reduction synergistically inhibits cancer cell migration and invasion.

Conclusions:

• EIF4G2 is a critical regulator of protein translation in HCC.
• The EIF4G2-PLEKHA1 axis represents a novel mechanism driving HCC progression.
• Targeting the EIF4G2-PLEKHA1 axis holds therapeutic potential for HCC treatment.