ZNF165 Is Involved in the Regulation of Immune Microenvironment and Promoting the Proliferation and Migration of Hepatocellular Carcinoma by AhR/CYP1A1

J Immunol Res. 2022 Jun 1:2022:4446805. doi: 10.1155/2022/4446805. eCollection 2022.

Abstract

The strong tumorigenic capacity and treatment resistance made hepatocellular carcinoma (HCC) a huge threat to public health. ZNF165, the kruppel family of zinc-finger-containing transcription factors, is expressed in HCC; however, its specific role in HCC and the molecular mechanism are yet to be elucidated. In this study, we observed that ZNF165 was overexpressed in liver cancer tissues and the immune microenvironment; higher ZNF165 expression was correlated with lower overall survival in liver cancer patients. The ZNF165 knockdown in Bel7402 cells revealed the impairment of the tryptophan/kynurenine/AhR/CYP1A1 axis. Moreover, the knockdown of CYP1A1 significantly inhibited the proliferation and migration of HCC cells, and ZNF165 promoted the transcriptional activity of AhR by facilitating the nuclear translocation of CYP1A1. In conclusion, the present study argued that ZNF165 was highly expressed in liver tissues and the immune microenvironment. ZNF165 promoted the proliferation and migration of HCC cells by activating the tryptophan/kynurenine/AhR/CYP1A1 axis and promoting the expression of CYP1A1.

MeSH terms

  • Carcinoma, Hepatocellular*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kynurenine / metabolism
  • Liver Neoplasms* / pathology
  • Tryptophan / metabolism
  • Tumor Microenvironment

Substances

  • DNA-Binding Proteins
  • ZNF165 protein, human
  • Kynurenine
  • Tryptophan
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1