Molecular mechanisms of mTOR-mediated cisplatin response in tumor cells DOI Creative Commons

Amirhosein Maharati,

Yasamin Rajabloo,

Meysam Moghbeli

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 11(1), P. e41483 - e41483

Published: Dec. 25, 2024

Cisplatin (CDDP) is one of the main chemotherapeutic drugs that widely used in many cancers. However, CDDP resistance a frequent therapeutic challenge reduces prognosis cancer patients. Since, has noticeable side effects normal tissues and organs, it necessary to assess molecular mechanisms associated with improve methods Drug efflux, detoxifying systems, DNA repair mechanisms, drug-induced apoptosis are involved multidrug CDDP-resistant tumor cells. Mammalian target rapamycin (mTOR), as serine/threonine kinase pivotal role various cellular such autophagy, metabolism, drug cell proliferation. Although, mTOR mainly activated by PI3K/AKT pathway, can also be regulated other signaling pathways. PI3K/Akt/mTOR axis functions key modulator unfavorable different Regarding, response, present review we discussed regulate mediated response

Language: Английский

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma DOI Open Access

HONGMIN CAO,

Ying Xue, Fei Wang

et al.

Biocell, Journal Year: 2024, Volume and Issue: 48(3), P. 473 - 490

Published: Jan. 1, 2024

Background: Cytotoxic T lymphocytes (CD8+ T) cells function critically in mediating anti-tumor immune response cancer patients.Characterizing the specific functions of CD8+ lung adenocarcinoma (LUAD) could help better understand local responses and estimate effect immunotherapy.Methods: Gens related to were identified by cluster analysis based on single-cell sequencing data three LUAD tissues their paired normal tissues.Weighted gene co-expression network (WGCNA), consensus clustering, differential expression analysis, least absolute shrinkage selection operator (LASSO) Cox regression conducted classify molecular subtypes for develop a risk model using prognostic genes cells.Expression model, effects tumor cell invasion, interactions with verified experiments.Results: This study defined two clusters 0 1) cells, being significantly associated prognosis LUAD.Three heterogeneous (clusters 1, 2, 3) differing prognosis, genome mutation events, status categorized 42 genes.A created 11 significant (including CD200R1, CLEC17A, ZC3H12D, GNG7, SNX30, CDCP1, NEIL3, IGF2BP1, RHOV, ABCC2, KRT81) was able independently death patients different cohorts.Moreover, also showed general applicability external validation cohorts.Low-risk benefit more from taking immunotherapy resistance anticancer drugs.The results experiments demonstrated that SNX30 downregulated, while ABCC2 KRT81 upregulated cells.Inhibition CD200R1 greatly increased invasiveness but inhibiting CDCP1 weakened invasion ability cells.Conclusion: classified LUAD.A predictive potential developed.

Language: Английский

Citations

10
A comprehensive review of the PTEN/PI3K/Akt axis in multiple myeloma: from molecular interactions to potential therapeutic targets DOI
Mina Alimohammadi,

Payman Rahimzadeh,

Ramin Khorrami

et al.

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155401 - 155401

Published: June 17, 2024

Language: Английский

Citations

9
Transcription Factor MAZ Potentiates the Upregulated NEIL3-mediated Aerobic Glycolysis, thereby Promoting Angiogenesis in Hepatocellular Carcinoma DOI

Fabiao Zhang,

Binfeng Wang, Wenlong Zhang

et al.

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

Citations

6
Hyaluronic acid-empowered nanotheranostics in breast and lung cancers therapy DOI

Fahad Alsaikhan

Environmental Research, Journal Year: 2023, Volume and Issue: 237, P. 116951 - 116951

Published: Aug. 24, 2023

Language: Английский

Citations

12
New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis DOI
Mehrdokht Sadrkhanloo, Mahshid Deldar Abad Paskeh, Mehrdad Hashemi

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 251, P. 154902 - 154902

Published: Oct. 21, 2023

Language: Английский

Citations

11
Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer DOI Open Access
Lang Chen, Xuan Huan,

Xidan Gao

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5722 - 5722

Published: Nov. 22, 2022

The accumulation of oxidative DNA base damage can severely disrupt the integrity genome and is strongly associated with development cancer. glycosylase critical enzyme that initiates excision repair (BER) pathway, recognizing excising damaged bases. Nei endonuclease VIII-like 3 (NEIL3) an emerging essential in maintaining stability. With in-depth study structure function NEIL3, we found it has properties related to process repair. For example, not only prefers single-stranded (ssDNA), G-quadruplex interstrand crosslinks (ICLs), but also participates maintenance replication fork stability telomere integrity. In addition, NEIL3 progression cancers cardiovascular neurological diseases, incredibly significantly overexpressed cancers, may become independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA exon-encoded origin by promotes multiple cancers. this review, have summarized characteristics damage. We focused on circNEIL3 development, prognosis.

Language: Английский

Citations

12
Identification of disulfidptosis-related subgroups and prognostic signatures in lung adenocarcinoma using machine learning and experimental validation DOI Creative Commons
Yuzhi Wang, Yunfei Xu,

Chunyang Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 20, 2023

Disulfidptosis is a newly identified variant of cell death characterized by disulfide accumulation, which independent ATP depletion. Accordingly, the latent influence disulfidptosis on prognosis lung adenocarcinoma (LUAD) patients and progression tumors remains poorly understood.We conducted multifaceted analysis transcriptional genetic modifications in regulators (DRs) specific to LUAD, followed an evaluation their expression configurations define DR clusters. Harnessing differentially expressed genes (DEGs) from these clusters, we formulated optimal predictive model amalgamating 10 distinct machine learning algorithms across 101 unique combinations compute score (DS). Patients were subsequently stratified into high low DS cohorts based median values. We then performed exhaustive comparison between cohorts, focusing somatic mutations, clinical attributes, tumor microenvironment, treatment responsiveness. Finally, empirically validated biological implications critical gene, KYNU, through assays LUAD lines.We two clusters there great differences overall survival (OS) microenvironment. selected "Least Absolute Shrinkage Selection Operator (LASSO) + Random Survival Forest (RFS)" algorithm develop average C-index different cohorts. Our effectively high- low-DS subgroups, with this latter demonstrating superior OS, reduced mutational landscape, enhanced immune status, increased sensitivity immunotherapy. Notably, accuracy outperformed published signature features. using samples found that inhibiting KYNU suppressed cells proliferation, invasiveness, migration vitro.The DR-based scoring system developed enabled accurate prognostic stratification provides important insights molecular mechanisms strategies for LUAD.

Language: Английский

Citations

7
Integrating single-cell and bulk expression data to identify and analyze cancer prognosis-related genes DOI Creative Commons
S. Bao, Yaxin Fan,

Yichao Mei

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(4), P. e25640 - e25640

Published: Feb. 1, 2024

Compared with traditional evaluation methods of cancer prognosis based on tissue samples, single-cell sequencing technology can provide information cell type heterogeneity for predicting biomarkers related to prognosis. Therefore, the bulk and expression profiles breast normal cells were comprehensively analyzed identify malignant non-malignant markers construct a reliable model. We first screened highly differentially expressed genes from multiple tissues tissues, inferred malignancy data. Then we identified eight critical conduct Cox regression analysis, calculate polygenic risk score (PRS), verify predictive ability PRS in two data groups. The results show that divide patients into high-risk group low-risk group. is overall survival time relapse-free interval factor independent conventional clinicopathological characteristics. Breast usually regarded as relatively good In order further explore whether this workflow be applied poor prognosis, selected lung comparative study. also build reasonable model cancer. This study provides new insight practical source code research drug targets. It basis prediction, treatment response personalized treatment.

Language: Английский

Citations

2
Enhancing cisplatin drug sensitivity through PARP3 inhibition: The influence on PDGF and G-coupled signal pathways in cancer DOI Creative Commons
Ayşegül Varol, Sabine M. Klauck, Françoise Dantzer

et al.

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 398, P. 111094 - 111094

Published: June 1, 2024

Drug resistance poses a significant challenge in cancer treatment despite the clinical efficacy of cisplatin. Identifying and targeting biomarkers open new ways to improve therapeutic outcomes. In this study, comprehensive bioinformatic analyses were employed, including comparative analysis multiple datasets, evaluate overall survival mutation hotspots 27 base excision repair (BER) genes more than 7,500 tumors across 23 types. By using various parameters influencing patient survival, revealing that overexpression 15 distinct BER genes, particularly PARP3, NEIL3, TDG, consistently correlated with poorer factors such as race, gender, metastasis. Single nucleotide polymorphism (SNP) within protein-coding regions highlighted potential deleterious effects mutations on protein structure function. The investigation proteins identified PARP3 due its high frequency. Moving from bioinformatics wet lab experiments, cytotoxic experiments demonstrated absence by CRISPR/Cas9-mediated knockdown MDA-MB-231 breast cells increased drug activity towards cisplatin, carboplatin, doxorubicin. Pathway indicated impact platelet-derived growth factor (PDGF) G-coupled signal pathways cisplatin exposure. PDGF, critical regulator cellular functions, was downregulated suggesting role progression. Moreover, influence G protein-coupled receptors (GPCRs) affects their function presence conclusion, study synthetic lethal interaction between GPCRs, PDGF signaling pathways, gene silencing. emerged promising target.

Language: Английский

Citations

2
NEIL3 promotes cell proliferation of ccRCC via the cyclin D1-Rb-E2F1 feedback loop regulation DOI
Mengzhao Zhang, Yunzhong Jiang, Jichang Wang

et al.

DNA repair, Journal Year: 2023, Volume and Issue: 133, P. 103604 - 103604

Published: Nov. 18, 2023

Language: Английский

Citations

3