The bioinformatics analysis and experimental validation of the carcinogenic role of EXO1 in lung adenocarcinoma DOI Creative Commons

Bohao Sun,

Jing Zhang, Nan Wang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 24, 2024

Background Exonuclease 1 (EXO1), a protein involved in mismatch repair and recombination processes, has been identified as prognostic biomarker lung adenocarcinoma (LUAD). Nevertheless, its role LUAD progression remains elusive. This study seeks to elucidate the functional significance of EXO1 evaluate potential therapeutic target. Materials methods Patient RNA-seq clinical data were acquired from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. Subsequently, protein-protein interaction (PPI) network was constructed using differentially expressed genes (DEGs) identify pivotal genes. Validation expression signature carried out through quantitative real-time PCR (qRT-PCR). Additionally, association between investigated. Immunohistochemistry utilized assess 93 cases invasive pulmonary adenocarcinoma. Finally, cellular assays conducted investigate impact on cells. Results Ten key molecules (PBK, ASPM, NCAPG, EXO1, MKI67, RRM2, AURKA, DLGAP5, UBE2C, CDC6) exhibited significantly elevated levels tissues. Moreover, gene correlated strongly with advanced T, N, M stages associated immune cell infiltration LUAD. Furthermore, marked increases observed patients diagnosed Notably, who increased lymph node metastasis, pleural invasion, poor tumor differentiation, stage. this employed wound healing assay CCK-8 proliferation significant promoting growth migration Conclusions ten hub initiation may serve marker for patients, offering new perspectives treatments.

Language: Английский

PARPi, BRCA, and gaps: controversies and future research DOI Creative Commons
Diego Dibitetto, Carmen A. Widmer, Sven Rottenberg

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(9), P. 857 - 869

Published: July 14, 2024

In recent years, various poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have been approved for the treatment of several cancers to target vulnerability homologous recombination (HR) deficiency (e.g., due BRCA1/2 dysfunction). this review we analyze ongoing debates and breakthroughs in use PARPis BRCA1/2-deficient cancers, juxtaposing 'double-strand break (DSB)' 'single-stranded DNA (ssDNA) gap' models synthetic lethality induced by PARPis. We spotlight complexity interaction, highlighting emerging research on role theta (POLθ) ssDNA gaps shaping therapy responses. scrutinize clinical ramifications these findings, especially concerning PARPi efficacy resistance mechanisms, underscoring heterogeneity BRCA-mutated tumors urgent need advanced bridge gap between laboratory patient outcomes.

Language: Английский

Citations

10
Targeting FEN1/EXO1 to enhance efficacy of PARP inhibition in triple-negative breast cancer DOI

Mallory I. Frederick,

Elicia Fyle,

Anna Clouvel

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 54, P. 102337 - 102337

Published: March 6, 2025

Language: Английский

Citations

0
CRISPR/Cas technologies for cancer drug discovery and treatment DOI
Kevin Chang Wang,

Thomas M Zheng,

Basil P. Hubbard

et al.

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Targeting Cellular DNA Damage Response in Cancer and Bacterial Infections: Current Progress, Challenges, and Opportunities DOI
Rongbo Lin, Xu Zhang,

Qinwei Zhu

et al.

Published: April 3, 2025

Review Targeting Cellular DNA Damage Response in Cancer and Bacterial Infections: Current Progress, Challenges, Opportunities Ranxun Lin 1, Xu Zhang Qinwei Zhu Xuening Chen Dai Longheng Li Zuoan 2, Zhonghui 1,* 1 College of Chemistry, Fuzhou University, 350108, China 2 Shengli Clinical Medical Fujian Department Emergency, Provincial Hospital, University Affiliated Key Laboratory Emergency Medicine, * Correspondence: [email protected] Received: 20 November 2024; Revised: 30 December Accepted: 21 February 2025; Published: 3 April 2025 Abstract: Effective cancer treatment remains challenging due to the genomic instability tumors frequent emergence resistance. Traditional approaches such as radiotherapy, chemotherapy, immunotherapy face limitations addressing tumor heterogeneity resistance mechanisms. damage response (DDR) pathway has emerged an innovative strategy, either monotherapy or combination with conventional treatments. DDR-targeted therapies, including poly-ADP-ribose polymerase (PARP) inhibitors, have shown promise reducing growth enhancing patient outcomes. Emerging targets ATM, ATR, CHK1/2, WRN, PARG, coupled cutting-edge technologies like CRISPR proteolysis-targeting chimeras (PROTACs), opened new avenues for precise effective treatment. Furthermore, combining DDR inhibitors established immune checkpoint demonstrated synergistic benefits, improving therapeutic efficacy overcoming Beyond cancer, also offer potential combat bacterial pathogens by exploiting vulnerabilities microbial repair systems. This review focuses on major advantages, challenges, future directions therapies infections. We discuss integration these traditional approaches, highlighting their enhance outcomes across diverse applications.

Language: Английский

Citations

0
PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer DOI Creative Commons
Ramya Ravindranathan, Ozge Somuncu, Alexandre André Balieiro Anastácio da Costa

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(47)

Published: Nov. 15, 2024

Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair by removal of poly (PAR) from PARylated proteins. Loss or inhibition PARG results in replication stress and sensitizes cancer cells to DNA-damaging agents. inhibitors are now undergoing clinical development for patients having tumors with homologous recombination deficiency (HRD), such as germline somatic

Language: Английский

Citations

1
Identification of EXO1 as a potential biomarker associated with prognosis and tumor immune microenvironment for specific human cancers DOI

Jingyun Wang,

Fen Liu,

Jianfu Heng

et al.

Mammalian Genome, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Language: Английский

Citations

1
Intrinsic PARG inhibitor sensitivity is mimicked by TIMELESS haploinsufficiency and rescued by nucleoside supplementation DOI Creative Commons
Camilla Coulson‐Gilmer, Samantha Littler, Bethany M. Barnes

et al.

NAR Cancer, Journal Year: 2024, Volume and Issue: 6(3)

Published: July 9, 2024

A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced inhibition

Language: Английский

Citations

0
Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents DOI
Rocco Caggiano, Evgeniia Prokhorova, Lena Duma

et al.

Neoplasia, Journal Year: 2024, Volume and Issue: 59, P. 101092 - 101092

Published: Nov. 30, 2024

Language: Английский

Citations

0
The bioinformatics analysis and experimental validation of the carcinogenic role of EXO1 in lung adenocarcinoma DOI Creative Commons

Bohao Sun,

Jing Zhang, Nan Wang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 24, 2024

Background Exonuclease 1 (EXO1), a protein involved in mismatch repair and recombination processes, has been identified as prognostic biomarker lung adenocarcinoma (LUAD). Nevertheless, its role LUAD progression remains elusive. This study seeks to elucidate the functional significance of EXO1 evaluate potential therapeutic target. Materials methods Patient RNA-seq clinical data were acquired from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. Subsequently, protein-protein interaction (PPI) network was constructed using differentially expressed genes (DEGs) identify pivotal genes. Validation expression signature carried out through quantitative real-time PCR (qRT-PCR). Additionally, association between investigated. Immunohistochemistry utilized assess 93 cases invasive pulmonary adenocarcinoma. Finally, cellular assays conducted investigate impact on cells. Results Ten key molecules (PBK, ASPM, NCAPG, EXO1, MKI67, RRM2, AURKA, DLGAP5, UBE2C, CDC6) exhibited significantly elevated levels tissues. Moreover, gene correlated strongly with advanced T, N, M stages associated immune cell infiltration LUAD. Furthermore, marked increases observed patients diagnosed Notably, who increased lymph node metastasis, pleural invasion, poor tumor differentiation, stage. this employed wound healing assay CCK-8 proliferation significant promoting growth migration Conclusions ten hub initiation may serve marker for patients, offering new perspectives treatments.

Language: Английский

Citations

0