Zinc finger protein 703 induces EMT and sorafenib resistance in hepatocellular carcinoma by transactivating CLDN4 expression
Open Access
- 8 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (4), 1-15
- https://doi.org/10.1038/s41419-020-2422-3
Abstract
Metastasis is one of the most common reasons of hepatocellular carcinoma (HCC) death; however, the molecular mechanism underlying HCC metastasis remains incompletely defined. Here we report a new function of Zinc Finger Protein 703 (ZNF703), a member of the NET/NlZ family of zinc finger transcription factors, in promoting hepatocellular carcinoma metastasis. We demonstrated that the overexpression of ZNF703 in human HCC tissue is correlated with tumor metastasis and recurrence, it is also related with the prognosis and survival rate of patients. ZNF703 overexpression promotes HCC progression in vitro and in vivo, whereas ZNF703 knockdown has the opposite effect. In addition, ZNF703 induces epithelialmesenchymal transition (EMT) via directly binding to the CLDN4 promoter and transactivating CLDN4 expression. Downregulation of CLDN4 can attenuate ZNF703-mediated HCC metastasis, whereas upregulation of CLDN4 can reverse the decreased metastasis induced by ZNF703 knockdown. Our data revealed that ZNF703 expression is correlated with CLDN4 level, the overexpression of both ZNF703 and CLDN4 are leaded to poorer prognosis of patients with HCC. Moreover, ZNF703 knockdown can enhance the sensitivity of HCC cell to sorafenib, whereas ZNF703 overexpression has the opposite effect. These results suggested that ZNF703 might be a potential target for cancer therapies and a candidate prognostic biomarker for predicting whether patients with HCC are befitting for sorafenib treatment.Keywords
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