Graduate School of Dalian Medical University, Dalian, Liaoning 116044, China.
Department of General Surgery & Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy, Xueyuan Road 1098, 518055 Shenzhen, China.
J Immunol Res. 2022 Jun 1;2022:4446805. doi: 10.1155/2022/4446805. eCollection 2022.
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.
肝癌（HCC）具有较强的致瘤能力和治疗耐药性，对公众健康构成巨大威胁。锌指蛋白 165（ZNF165）是含锌指的 Kruppel 家族转录因子，在 HCC 中表达；但其在 HCC 中的具体作用及其分子机制尚不清楚。本研究观察到 ZNF165 在肝癌组织和免疫微环境中过度表达；ZNF165 高表达与肝癌患者总体生存率降低相关。在 Bel7402 细胞中敲低 ZNF165 会破坏色氨酸/犬尿氨酸/AhR/CYP1A1 轴。此外，敲低 CYP1A1 可显著抑制 HCC 细胞的增殖和迁移，ZNF165 通过促进 CYP1A1 的核易位来增强 AhR 的转录活性。总之，本研究表明 ZNF165 在肝组织和免疫微环境中高表达。ZNF165 通过激活色氨酸/犬尿氨酸/AhR/CYP1A1 轴并促进 CYP1A1 的表达，促进 HCC 细胞的增殖和迁移。
