Toxic Effects of Tetrabromobisphenol A on Human Hepatocellular Carcinoma Cells(HepG2) Evaluated Using RNA-Seq

Abstract

Tetrabromobisphenol A(TBBPA) is used as a brominated flame retardant and can easily release into environment. It has been detected in a variety of environmental media and even in food, making it a new pollutant that is potentially harmful to environment and human health. However, the toxicity and underlying mechanism of TBBPA remain to be explored. TBBPA is actively metabolized in the liver, so it is vital to study the hepatocellular toxicity of TBBPA. In this study, we treated hepatocellular carcinoma cells(HepG2) with TBBPA and searched the differentially expressed genes(DEGs) triggered by TBBPA exposure. RNA-seq analysis showed that the expression of genes, such as CLIC1 and GATSL1, were significantly down-regulated and PTENP1 was significantly up-regulated after TBBPA exposure, and these genes were involved in cell proliferation and metabolism. The down-regulated genes were enriched to peroxisome proliferator-activated receptor(PPAR) signaling pathway and up-regulated genes were enriched to Janus Kinase-signal transduces and activators of transcription(JAK-STAT) signaling pathway, which play a role in regulating cell growth. Overall, our transcriptome analysis obtained for TBBPA-treated HepG2 cells implies that TBBPA affects the cell proliferation and growth.

Keywords

Tetrabromobisphenol A / Hepatocellular carcinoma / Cytotoxicity / RNA-seq

References

[1] Liu K, Li J, Yan S J, Zhang W, Li Y J, Han D. Chemosphere, 201, 148: 8.

[2] Yann G, Dana L, Kathryn Z G, Fatiha E G, Veronique B, Lamia B T, Heidi M, Kurt S. Lancet Oncol., 201, 17: 419.

[3] Mohamed A A. Environ. Int., 201, 94: 235.

[4] Yang S W, Wang S R, Liu H L, Yan Z G. Environ. Sci. Pollut. Res., 2012, 19: 4090.

[5] Joana F, Melissa M, Elisa C. Environ. Pollut., 2021, 285: 117475.

[6] Linda S B, Ake B. Environ. Health Perspect., 2010, 118: A514.

[7] Juliette L. Chemosphere, 2008, 73: 216.

[8] Ahmedin J, Freddie B, Melissa M C, Jacques F, Elizabeth W, David F. CA Cancer J. Clin., 2011, 61: 69.

[9] Gu X S, Manautou J E. Expert Rev. Mol. Med., 2012, 14: e4.

[10] Kim U J, Oh J E. Environ. Pollut., 2014, 184: 193.

[11] Yu Y J, Hao C J, Xiang M D, Tian J L, Kuang H X, Li Z C. Sci. Total Environ., 2022, 832: 154847.

[12] Chi Q, Zhang W X, Wang L, Huang J, Yuan M, Xiao H M, Wang X. Chemosphere, 2019, 246: 1.

[13] Lyu L, Jin X J, Li Z Y, Liu S, Li Y, Su R J, Su H L. Ecotoxicol. Environ. Saf., 2020, 192: 110255.

[14] Jennifer J T, Jan K. J. Angiogenes Res., 2010, 2: 23.

[15] Kwang S S, Stuart H Y. Curr. Pharm. Des., 2005, 11: 2753.

[16] Mark A B, James R G. Cell Motil. Cytoskeleton, 2003, 56: 159.

[17] Wei X Y, Li J, Xie H Y, Wang H X, Wang J G, Zhang X Y, Zhuang R Z, Lu D, Ling Q, Zhou L, Xu X, Zheng S S. J. Gastroenterol Hepatol., 2014, 30: 208.

[18] Jacek L, Elzbieta Z, Dominik D, Jerzy W L. NeuroToxicology, 2017, 63: 126.

[19] Linde D, Ellen W, Tom V B, Peter V. Microbes Infect., 2009, 11: 1050.

[20] Tian T, Nan K J, Guo H, Wang W J, Ruan Z P, Wang S H, Liang X, Lu C X. Oncol. Rep., 2010, 23: 1593.

[21] Chen C L, Tseng Y W, Wu J C, Chen G Y, Lin K C, Hwang S M, Hu Y C. Biomaterials, 2015, 44: 71.

[22] Qian Y Y, Li K, Liu Q Y, Liu Z S. Oncotarget, 2018, 8: 107859.

[23] Shi L K, Karrar E, Wang X G. J. Food Biochem., 2021, 45: 1.

[24] Tommaso M, Maria M, Andrea G. PPAR Res., 201, 2016: 1.

[25] Kisseleva T, Bhattacharya S, Braunstein J, Schindler C W. Gene, 2002, 285: 1.