General Transcription Factor IIB Overexpression and a Potential Link to Proliferation in Human Hepatocellular Carcinoma

Abstract

The general transcription factor IIB (TFIIB) plays a central role in preinitiation complex (PIC) assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II (RNA POLII). TFIIB functionally counteracts the transcriptional activation of hepatitis B virus X protein (HBx), which has been shown to play a role in the development of human hepatocellular carcinoma (HCC). However, the function of TFIIB in HCC remains unclear. In this article, we demonstrate that TFIIB plays an important role in HCC pathogenesis. TFIIB expression was immunohistochemically examined in a series of 100 HCC tissue specimens. The expression level of TFIIB showed significant correlation with the histological grade (P = 0.030), the level of AFP (P = 0.011) and the proliferation marker Ki-67 (P = 0.0002). High TFIIB expression level correlated with poor survival. Western blot analysis also confirmed that the TFIIB protein was overexpressed in HCC tissue compared to benign normal tissue. Additionally, Western blot and qRT-PCR analyses showed a high expression level of TFIIB protein in the HCC cell lines SMMC7721, HepG2, BEL7404, and Huh7 and the immortalized normal line BEL7702 but a lower expression in the normal Chang hepatocyte cell line. Following the release of Huh7 cells from serum starvation, the expression of TFIIB was upregulated. A cell growth assay suggested that TFIIB was involved in the proliferation and growth of HCC cells. In conclusion, our results demonstrate that TFIIB overexpression may play essential roles in the pathogenesis of hepatocellular carcinoma by affecting the proliferation of HCC cells.