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

Liu, Peng; Zhou, Yan; Dong, Xin; Zheng, Biao; Liang, Bo; Liang, Rui; Liu, Zhong; Li, Li; Gong, Peng

doi:10.1155/2022/4446805

Cited by 4 publications

(4 citation statements)

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“…constructed a risk model based on CHMP4C to predict the tumor immune microenvironment (TIME) and guide the chemotherapy and immunotherapy of BLCA ( 42 ). ZNF165 is a functionally enigmatic cancer/testis (CT) antigen whose expression is usually restricted to germ cells but is aberrantly activated in tumors and is associated with the prognosis of a variety of tumors, mediated mainly by participating in the regulation of the TIME ( 43 , 44 ). STAP2 promotes the generation of long-term functional memory CD8+ T cells by preventing terminal effector differentiation ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA

Xue

Zhao

et al. 2023

Front. Oncol.

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IntroductionThe prognosis of bladder cancer (BLCA) and response to immune checkpoint inhibitors (ICIs) are determined by multiple factors. Existed biomarkers for predicting the effect of immunotherapy cannot accurately predict the response of BLCA patients to ICIs.MethodsTo further accurately stratify patients’ response to ICIs and identify potential novel predictive biomarkers, we used the known T cell exhaustion (TEX)-related specific pathways, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-g, and T- cell cytotoxicpathways, combined with weighted correlation network analysis (WGCNA) to analyze the characteristics of TEX in BLCA in detail, constructed a TEX model.ResultsThis model including 28 genes can robustly predict the survival of BLCA and immunotherapeutic efficacy. This model could divide BLCA into two groups, TEXhigh and TEXlow, with significantly different prognoses, clinical features, and reactivity to ICIs. The critical characteristic genes, such as potential biomarkers Charged Multivesicular Body Protein 4C (CHMP4C), SH2 Domain Containing 2A (SH2D2A), Prickle Planar Cell Polarity Protein 3 (PRICKLE3) and Zinc Finger Protein 165 (ZNF165) were verified in BLCA clinical samples by real-time quantitative chain reaction (qPCR) and immunohistochemistry (IHC).DiscussionOur findings show that the TEX model can serve as biological markers for predicting the response to ICIs, and the involving molecules in the TEX model might provide new potential targets for immunotherapy in BLCA.

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Section: Discussionmentioning

confidence: 99%

Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA

Xue

Zhao

et al. 2023

Front. Oncol.

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“…We then assessed the transcriptional activity of the CYP1A1 promoter using a dual luciferase reporter assay and found enhanced transcriptional activity of CYP1A1 in the PM2.5 exposed cells compared with the control cells ( Figure 9B ). Previous studies have shown that the expression of some cytochrome P450 family genes are regulated by transcription factors (TFs) ( Degrelle et al, 2022 ; Liu et al, 2022 ; Rannug, 2022 ; Shivaram et al, 2023 ). Thus, whether PM2.5 modified CYP1A1 expression via TFs in trophoblast cells was assessed.…”

Section: Resultsmentioning

confidence: 99%

PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis

Li,

Zhang

et al. 2023

eLife

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Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal number and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies.

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“…The characterization of tryptophan metabolism and its dysregulation in fibroids revealed an increased expression of CYP1B1 mRNA, a marker of AhR activation [ 88 , 94 ]. ZNF165 (a member of the Kruppel family of zinc-finger-containing transcription factors), which is overexpressed in liver cancer tissues and the immune microenvironment, promotes the proliferation and migration of hepatocellular carcinoma by activating the tryptophan/kynurenine/AhR/CYP1A1 axis and by boosting the expression of CYP1A1 [ 95 ].…”

Section: Gut Microbiota Indole Products and Their Interaction With Cy...mentioning

confidence: 99%

The Engagement of Cytochrome P450 Enzymes in Tryptophan Metabolism

et al. 2023

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Tryptophan is metabolized along three main metabolic pathways, namely the kynurenine, serotonin and indole pathways. The majority of tryptophan is transformed via the kynurenine pathway, catalyzed by tryptophan-2,3-dioxygenase or indoleamine-2,3-dioxygenase, leading to neuroprotective kynurenic acid or neurotoxic quinolinic acid. Serotonin synthesized by tryptophan hydroxylase, and aromatic L-amino acid decarboxylase enters the metabolic cycle: serotonin → N-acetylserotonin → melatonin → 5-methoxytryptamine→serotonin. Recent studies indicate that serotonin can also be synthesized by cytochrome P450 (CYP), via the CYP2D6-mediated 5-methoxytryptamine O-demethylation, while melatonin is catabolized by CYP1A2, CYP1A1 and CYP1B1 via aromatic 6-hydroxylation and by CYP2C19 and CYP1A2 via O-demethylation. In gut microbes, tryptophan is metabolized to indole and indole derivatives. Some of those metabolites act as activators or inhibitors of the aryl hydrocarbon receptor, thus regulating the expression of CYP1 family enzymes, xenobiotic metabolism and tumorigenesis. The indole formed in this way is further oxidized to indoxyl and indigoid pigments by CYP2A6, CYP2C19 and CYP2E1. The products of gut-microbial tryptophan metabolism can also inhibit the steroid-hormone-synthesizing CYP11A1. In plants, CYP79B2 and CYP79B3 were found to catalyze N-hydroxylation of tryptophan to form indole-3-acetaldoxime while CYP83B1 was reported to form indole-3-acetaldoxime N-oxide in the biosynthetic pathway of indole glucosinolates, considered to be defense compounds and intermediates in the biosynthesis of phytohormones. Thus, cytochrome P450 is engaged in the metabolism of tryptophan and its indole derivatives in humans, animals, plants and microbes, producing biologically active metabolites which exert positive or negative actions on living organisms. Some tryptophan-derived metabolites may influence cytochrome P450 expression, affecting cellular homeostasis and xenobiotic metabolism.

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

Cited by 4 publications

References 24 publications

Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA

Construction of T cell exhaustion model for predicting survival and immunotherapy effect of bladder cancer based on WGCNA

PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis

The Engagement of Cytochrome P450 Enzymes in Tryptophan Metabolism

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