TAZ-regulated expression of IL-8 is involved in chemoresistance of hepatocellular carcinoma cells.

Hao Zhang, Qiao-Ling Yu, Lin Meng, Hong Huang, Hui Liu, Na Zhang, Na Liu, Jun Yang, Yuan-Zhen Zhang, Qiang Huang

Archives of biochemistry and biophysics 2020 Oct 30

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Chemotherapy resistance is one of the major challenges for the treatment of hepatocellular carcinoma (HCC). In order to investigate the mechanisms involved in chemoresistance of HCC, we established cisplatin (CDDP) and doxorubicin (Dox) resistant HCC cells. The expression of transcriptional coactivator with PDZ-binding motif (TAZ), one of the major downstream effectors of Hippo pathway, was upregulated in chemoresistant HCC cells. Targeted inhibition of TAZ via its siRNAs can restore CDDP and Dox sensitivity of chemoresistant HCC cells. The upregulation of TAZ increased the expression of IL-8 in HCC/CDDP and HCC/Dox cells. Recombinant IL-8 (rIL-8) antagonized the increased chemosensitivity mediated by TAZ knockdown. Mechanistically, TAZ can directly bind with the promoter of IL-8 to activate its transcription in chemoresistant HCC cells. Collectively, our data showed that TAZ-regulated expression of IL-8 was involved in chemoresistance of HCC cells. It indicated that targeted inhibition of TAZ/IL-8 axis might be helpful to improve chemotherapy efficiency for HCC. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Hao Zhang, Qiao-Ling Yu, Lin Meng, Hong Huang, Hui Liu, Na Zhang, Na Liu, Jun Yang, Yuan-Zhen Zhang, Qiang Huang. TAZ-regulated expression of IL-8 is involved in chemoresistance of hepatocellular carcinoma cells. Archives of biochemistry and biophysics. 2020 Oct 30;693:108571