CYP2C9 inhibits the invasion and migration of esophageal squamous cell carcinoma via downregulation of HDAC

Abstract

Cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of cancer drugs and exogenous carcinogens. In our study, CYP2C9 was downregulated in multiple cohorts of human esophageal squamous cell carcinoma (ESCC). Until now, its role and epigenetic regulation of CYP2C9 repression in ESCC remain poorly understood. CYP2C9 repression in collected ESCC patient tumor tissues was demonstrated by RT-qPCR and Western blot. The histone acetylation level was carried out by the treatment of histone deacetylase inhibitor TSA and RNA interference. Epigenetic analysis revealed that the increased expression of CYP2C9 in KYSE-150 and TE1 cells was characterized by inhibition of HDAC8 and HDAC1, respectively. TSA decreased the levels of HDAC occupancy around CYP2C9 promoter region greatly. Overexpression of CYP2C9 reduced the invasion and migration of ESCC cells.

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Data availability

The datasets obtained and analyzed during the current study were available from the corresponding authors in a reasonable request.

Abbreviations

ESCC:

Esophageal squamous cell carcinoma

CYP2C9:

Cytochrome P450 2C9

HDAC:

Histone deacetylase

siRNAs:

Small interfering RNAs

FCM:

Flow Cytometry

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Funding

This work was financially supported by National Natural Science Foundation of China (No. 81702801), Hangzhou City Scientific Technology Research Foundation of Zhejiang Province, China (No. 20180533B67), China Postdoctoral Science Foundation (No. 2020M680130), Zhejiang Provincial Natural Sciences Foundation of China (No. LY18H310012), and Zhejiang Provincial Natural Sciences Foundation of China (No. LGF19H310001).

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Contributions

ZJ and XZ performed most of the experiments and wrote the manuscript. MJ and WW wrote and revised a part of the manuscript. LQ and LY performed Western blotting and qRT-PCR analysis. YH designed and supervised the study.

Corresponding author

Correspondence to Yuhui Hua.

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The authors declare that they have no potential or actual conflicts of interest.

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This project was approved by the Institutional Review Board of Hangzhou Cancer Hospital (Permit Number: HZCH-2016-02).

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Jiang, Z., Zheng, X., Wang, W. et al. CYP2C9 inhibits the invasion and migration of esophageal squamous cell carcinoma via downregulation of HDAC. Mol Cell Biochem (2021). https://doi.org/10.1007/s11010-021-04050-3

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Keywords

  • ESCC
  • CYP2C9
  • Histone acetylation
  • HDAC