Abstract 4936: The function role of Brf1 in alcohol-induced human and mouse hepatocellular carcinoma*

Abstract

Abstract Brf1 (TFIIB-related factor 1) specifically regulates the transcription of Pol III genes (RNA polymerase III-dependent genes), including tRNAs and 5S rRNAs, which are elevated in both transformed and tumor cells, suggesting that they play a crucial role in tumorigenesis. Our recent studies have demonstrated that alcohol consumption increases Brf1 expression and Pol III gene transcription to promote tumor development. However, it remains to be investigated that Brf1 is expressed in human cancers. At the present studies, we have determined the significance of Brf1 overexpression in human hepatocellular carcinoma (HCC) and the impaction of repressing Brf1 expression in alcohol-promoted cell transformation. Biopsies of human HCC, liver tumor samples of mice and cell lines of normal and tumor liver were utilized to determine alteration of Brf1 expression using cytological and molecular biological approaches. The result indicates that Brf1 expression is increased in human cases of HCC. High expression of Brf1 displays shorter overall survival period. Levels of Brf1 and Pol III gene transcription in HCC patients with alcohol consumption show an additional increase, compared with the cases of non-HCC with or without alcohol intake. Induction of Brf1 and Pol III genes by ethanol in hepatoma cells is higher than in non-tumor cells. Ethanol increases the rate of cell transformation. Repression of Brf1 inhibits alcohol-promoted cell transformation. Together, these studies demonstrate that Brf1 is overexpressed in HCC cases and liver tumor cell lines. High level of Brf1 in human HCC is correlated with short survival time. Alcohol consumption enhances Brf1 expression to promote cell transformation. Brf1 is a new biomarker of diagnosis and prognosis of HCC. *: The project is supported by NIH grants: AA017288, AA021114 and AA02324 to Shuping Zhong Citation Format: Shuping Zhong. The function role of Brf1 in alcohol-induced human and mouse hepatocellular carcinoma*. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4936.