The present work was performed to clarify the role of TATA-binding protein (TBP) in hepatocellular carcinoma (HCC). TBP expression in adjacent liver tissues and HCC tissue sample was detected by immunohistochemistry and qRT-PCR. With CCK-8, BrdU, flow cytometry, and transwell assays, the malignancy of cancer cell lines were evaluated. The binding sites of TBP and AKT serine/threonine kinase 3 (Akt3) promoter region were predicted by PROMO database, and the binding relationship between TBP and AKT3 promoter was verified with dual luciferase reporter gene assay and ChIP-qPCR assay. The effect of TBP on AKT3 expression was examined by immunoblotting. The signaling pathways associated with AKT3 were predicted by gene set enrichment analysis (GSEA) with LinkedOmics database. It was revealed that, TBP expression in HCC tissues and cell lines was up-regulated, which was associated with the short survival time of patients. Up-regulation of TBP promoted the viability and aggressiveness of HCC cells, while knockdown of TBP had opposite effects. TBP could bind with AKT3 promoter region, and TBP overexpression promoted the expression of AKT3, while its knockdown worked oppositely. Additionally, TBP/AKT3 axis modulated mTOR expression in HCC cells. In conclusion, TBP promotes the transcription of AKT3, thus accelerating the malignant progression of HCC.
Keywords: AKT3; HCC; TBP; apoptosis; invasion; migration; proliferation.
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