Transcription Factor MAZ Potentiates the Upregulated NEIL3-mediated Aerobic Glycolysis, thereby Promoting Angiogenesis in Hepatocellular Carcinoma

Current Cancer Drug Targets, Journal Year: 2024, Volume and Issue: 24(12), P. 1235 - 1249

Published: Feb. 13, 2024

Hepatocellular carcinoma (HCC) is characterized by high vascularity and notable abnormality of blood vessels, where angiogenesis a key process in tumorigenesis metastasis. The main functions Nei Like DNA Glycosylase 3 (NEIL3) include alcoholization repair, immune response regulation, nervous system development function, damage signal transduction. However, the underlying mechanism expression NEIL3 progression HCC whether absence or silencing inhibits cancer remain unclear. Therefore, deeper understanding mechanisms which increased promotes needed.

Language: Английский

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Myc-associated zinc finger protein: A “double-edged sword” in the malignant process of tumors

New discovery., Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: April 19, 2025

Myc-associated zinc finger protein (MAZ), a cysteine2-Histidine2 (C2H2)-type transcription factor, is widely expressed in human tissues and frequently dysregulated various malignancies, positioning it as promising target for cancer therapy. MAZ exerts dual regulatory effects on gene by binding to guanine-cytosine-rich (GC-rich) DNA sequences, modulating the of numerous genes. This review examines role progression hepatocellular carcinoma, breast cancer, renal pancreatic prostate other with focus recent advancements understanding its molecular mechanisms. These insights aim contribute development improved diagnostic therapeutic strategies cancer.

Language: Английский

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ANKRD22 Induced by Transcription Factor MAZ Promotes Proliferation and Invasion of Nasopharyngeal Carcinoma

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(5)

Published: May 1, 2025

ABSTRACT Nasopharyngeal carcinoma (NPC) is very common in Southeast China, with the characteristics of high aggression and metastasis. Ankyrin repeat domain‐containing protein 22 (ANKRD22) contributes to tumor growth different tumors, but its role NPC still unknown. This study set out address action ANKRD22 progression NPC. The expression was examined by reverse transcription quantitative polymerase chain reaction western blot. function addressed through Cell Counting Kit‐8, flow cytometry, transwell, luciferase, chromatin immunoprecipitation, blot assays. Besides, vivo assessed using immunohistochemistry terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assays after nude mice were administrated HK‐1 cells transfected sh‐ANKRD22. upregulated NPC, which predicted a poor prognosis patients. Knockdown suppressed invasion, enhanced apoptosis cells. Mechanically, MYC‐associated zinc finger (MAZ) factor that positively modulated MAZ/ANKRD22 axis accelerated proliferation repressed In vivo, silencing diminished size weight, Ki‐67 ANKRD22, increased transcriptionally MAZ, promoted

Language: Английский

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NEIL3 Deficiency Enhances HCC Cell Sensitivity to Oxaliplatin by Inhibiting the Fanconi Anaemia Pathway

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Despite some achievements in oxaliplatin‐based chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC), abnormal activation DNA damage repair pathways HCC cells remains a major problem, limiting efficacy chemotherapy. In previous study, we found that endonuclease VIII‐like protein 3 (NEIL3) is expressed high proportion patients with and associated an unfavourable prognosis. However, role NEIL3 chemoresistance still unclear. The aim this study was to evaluate whether how regulates oxaliplatin anti‐tumour efficacy. Gene expression after cell lines assessed by real‐time quantitative PCR, western blot analysis bioinformatics analysis. effect on regulating using counting kit‐8 assays, colony formation flow cytometry vivo nude mice study. Mechanistic insights into sensitivity mediated inhibition were obtained through immunofluorescence RNA sequencing analyses. Our findings demonstrated markedly downregulated administration. knockdown impaired viability increased apoptosis exposed oxaliplatin. addition, reduced tumour progression enhanced xenograft models. Furthermore, knocking down significantly oxaliplatin‐mediated Fanconi anaemia pathway. results revealed may be promising therapeutic target improving HCC.

Language: Английский

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Prognostic and immunological implications of heterogeneous cell death patterns in prostate cancer

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Aug. 24, 2024

Prostate cancer is one of the most common cancers in men with a significant proportion patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles tumor progression and can potentially serve as prognostic therapeutic biomarkers PCa. This study aimed develop signature for BCR PCa using PCD-related genes. We conducted an analysis 19 different modes PCD comprehensive model. Bulk transcriptomic, single-cell genomic, clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, GSE193337. analyzed expression mutations constructed, evaluated, validated Ten found be associated PCa, specific patterns exhibited by various components within microenvironment. Through Lasso Cox regression analysis, we established Cell Death Index (PCDI) utilizing 11-gene signature. High PCDI values five independent datasets increased risk patients. Notably, older age advanced T N staging higher values. By combining staging, constructed nomogram enhanced predictive performance. Additionally, high significantly correlated decreased drug sensitivity, drugs such Docetaxel Methotrexate. Patients lower demonstrated immunophenoscores (IPS), suggesting response rate immune therapy. Furthermore, was checkpoint genes key microenvironment, macrophages, cells, NK cells. Finally, specimens differential PCDI-related PCDRGs at both gene protein levels. In conclusion, developed novel PCD-based feature that successfully predicted provided insights into sensitivity potential These findings have implications treatment

Language: Английский

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Inhibition of demethylase by IOX1 modulates chromatin accessibility to enhance NSCLC radiation sensitivity through attenuated PIF1

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)

Published: Dec. 12, 2023

Abstract Chromatin accessibility is a critical determinant of gene transcriptional expression and regulated by histones modification. However, the potential for manipulating chromatin to regulate radiation sensitivity remains unclear. Our findings demonstrated that histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), could enhance radiosensitivity non-small cell lung cancer (NSCLC) in vitro vivo. Mechanistically, IOX1 treatment reduced promoter region DNA damage repair genes, leading decreased efficiency elevated induced γ irradiation. Notably, significantly both transcription phytochrome interacting factor 1 (PIF1), key player telomere maintenance. Inhibition PIF1 delayed radiation-induced telomeric repair, as well increased NSCLC Further study indicated above process was reduction myc-associated zinc finger protein (MAZ) binding distal intergenic PIF1. Taken together, IOX1-mediated inactivation accessibility, which partly due inhibition, thereby enhancing radiosensitivity.

Language: Английский

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RAG1/2 induces double‐stranded DNA breaks at non‐Ig loci in the proximity of single sequence repeats in developing B cells

European Journal of Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

In developing B cells, V(D)J gene recombination is initiated by the RAG1/2 endonuclease complex, introducing double-stranded DNA breaks (DSBs) in V, D, and J genes resulting formation of hypervariable parts immunoglobulins (Ig). Persistent or aberrant targeting a potential threat to genome integrity. While RAG1 RAG2 have been shown bind various regions genome-wide, vivo off-target damage instigated remains less well understood. current study, we identified containing RAG1/2-induced mouse pre-B cells on genome-wide scale using global DSB detection strategy. We detected 1489 putative RAG1/2-dependent DSBs, most which were located outside Ig loci. sequence motif analysis showed specific enrichment DSBs at GA- CA-repeats GC-rich motifs. These findings provide further insights into activity. The ability introduce non-Ig loci during endogenous emphasizes its genotoxic lymphocytes.

Language: Английский

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