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.

Pancreatic adenocarcinoma (PAAD) is the most common primary malignancy of the pancreas. Growing studies indicate that transcription factors (TFs) are abnormally expressed in PAAD. We, therefore, aimed to evaluate the effect of TFs in PAAD and develop a TF-based prognostic signature for the patients. The expression of the TFs and the clinical characteristics were obtained from TCGA datasets. The levels of the TFs were evaluated in PAAD tissues or nontumor tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to determine the potential function of the dysregulated TFs. To create a prognostic signature, we used univariate and multivariate Cox regression. In addition, the relationship between risk score and tumor microenvironment was analyzed. In this study, we observed 19 increased and 10 decreased TFs in PAAD tissues. KEGG assays indicated that dysregulated TFs were involved in transcriptional misregulation in cancer. Multivariate Cox analysis identified two prognostic factors, Zinc finger protein 488 and BCL11A; and we developed a risk score model by these two factors. The Kaplan-Meier estimator suggested that patients with high risk exhibited a shorter overall survival than those with low risk. The receiver operating characteristic curve proved that the accuracy of this prognostic signature was 0.686 in predicting the 5-year survival. In addition, we observed that the high score was distinctly related to advanced tumor stage and immune infiltrates. Taken together, we developed a novel TF-related model which could be applied as a potential prognostic tool for PAAD and may guide the choice of immunotherapies.