In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript a...In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues.Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells.Furthermore,EIF5B knockdown suppressed epithelial-mesenchymal transition(EMT)and the cancer stem cell(CSC)phenotype.Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil(5-FU).In the HCC cells,activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing.IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner.Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.展开更多
基金supported by National Natural Science Foundation of China(No.81773167)Project of Traditional Chinese Medicine of Guangdong Administration(No.20132155)Medical and Health Science and Technology Project of Guangzhou Baiyun District(No.2020-YL-002).
文摘In this study,we investigated the functional role of eukaryotic initiation factor 5B(EIF5B)in hepatocellular carcinoma(HCC)and the underlying mechanisms.Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues.Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells.Furthermore,EIF5B knockdown suppressed epithelial-mesenchymal transition(EMT)and the cancer stem cell(CSC)phenotype.Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil(5-FU).In the HCC cells,activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing.IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner.Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.
基金supported by the National Key R&D Program of China(2019YFA0906003)the National Natural Science Foundation of China(32000989)+5 种基金China Postdoctoral Science Foundation Grant(2020M682911 and 2020M670051ZX)Guangdong Special Support Program(2021JC06Y578)the Shenzhen Municipal Government of China(JCYJ20200109120016553,CJGJZD20200617102403009,and RCBS20210706092256081)the Sanming Project of Shenzhen Health and Family Planning Commission(SZSM202011017)Shenzhen Institute of Synthetic Biology Scientific Research Program(ZTXM20214005)the Shenzhen High-level Hospital Construction Fund。
