eIF3a is the largest subunit of eIF3 complex and is a key player in translational control. Recently eIF3a is recognized as a proto-oncogene, which is overexpressed and connected to tumorigenesis of many cancers. However, the mechanistic roles of eIF3a during the tumorigenesis remain largely elusive. Here, we report that depletion of eIF3a significantly reduced HIF1 alpha protein level and cellular glycolysis ability. Mechanistically, we found that eIF3a regulates HIF1 alpha protein synthesis through internal ribosomal entry site (IRES)-dependent translation. Importantly, through analyses of our own sample collection, we found that eIF3a is overexpressed in hepatocellular carcinoma (HCC) tissues, and a high level of eIF3a predicts poor prognosis of HCC patients. TCGA analyses further confirmed that eIF3a is coincident with an elevated activity of HIF1 alpha pathway genes. Collectively, we identify elF3a as a regulator for glycolysis through HIF1 alpha IRES-dependent translational regulation, which may be a potential therapeutic target for HCC.
[1]Fudan Univ, Dept Liver Surg & Transplantat,Inst Biomed Sci, Liver Canc Inst,Minist Educ,Key Lab Med Epigenet, Zhongshan Hosp,Key Lab Carcinogenesis & Canc Inva, Shanghai 200032, Peoples R China.
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