CYP19A1 regulates chemoresistance in colorectal cancer through modulation of estrogen biosynthesis and mitochondrial function DOI Creative Commons
Yang Wang, Qiang Ji, N. Cao

et al.

Cancer & Metabolism, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 28, 2024

Abstract Chemoresistance remains a major challenge in the effective treatment of colorectal cancer (CRC), contributing to poor patient outcomes. While molecular mechanisms underlying chemoresistance are complex and multifaceted, emerging evidence suggests that altered mitochondrial function hormone signaling play crucial roles. In this study, we investigated role CYP19A1, key enzyme estrogen biosynthesis, regulating CRC. Using combination vitro functional assays, transcriptomic analysis, clinical data mining, demonstrate CYP19A1 expression is significantly upregulated CRC cells patient-derived samples compared normal controls. Mechanistically, found regulates through modulation I activity, which mediated by CYP19A1-dependent biosynthesis. Notably, targeted inhibition using specific inhibitors effectively reversed chemotherapeutic drugs. Moreover, analysis TCGA dataset revealed high correlates with overall survival chemotherapy-treated patients. Taken together, our findings uncover novel for signaling, highlight potential targeting CYP19A1/estrogen/complex axis as therapeutic strategy overcome improve

Language: Английский

Structure–Activity Relationship of Hemicyanine Molecules: Mitochondrion-Targeting Hemicyanine Fluorescent Molecular Probes for HSO3– Recognition and Near-Infrared Image-Guided Photothermal/Photodynamic Synergetic Therapy DOI
Lu Zhang, Ke Yan,

Shuang Min

et al.

The Journal of Physical Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown, P. 1746 - 1752

Published: Feb. 10, 2025

Hemicyanine molecules have unparalleled potential in the fields of fluorescence sensing, bioimaging, and disease therapeutics due to their excellent optical properties, cell penetration, mitochondrial targeting, photosensitivity. Herein, three dual-cation hemicyanine molecular probes named DCy, PDCy, TDCy were developed. All them could detect HSO3-, PDCy recognize HSO3- under 365 nm ultraviolet light or sunlight. In addition, is a multifunctional molecule, which has following advantages: simple synthesis, red near-infrared dual-channel imaging, photothermal/photodynamic synergistic therapy capabilities. Upon analysis correlation between structures recognition, photosensitivity, photothermal activity, cytotoxicity, structure-activity relationship be summarized, provide guidance for subsequent research development.

Language: Английский

Citations

0
Integrative analysis of mitochondrial-related gene profiling identifies prognostic clusters and drug resistance mechanisms in low-grade glioma DOI Creative Commons

Xiaozan Chang,

Yingxuan Huang,

Ying Qu

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 5, 2025

Mitochondrial dysfunction has emerged as a critical factor in the progression and prognosis of low-grade glioma (LGG). In this study, we explored role mitochondrial-related genes through consensus clustering analysis using multi-omics data from TCGA, CGGA, other independent datasets. Patients were categorized into three clusters (Cluster A, B, C), with Cluster B consistently associated poorer prognosis. Mutation landscape revealed distinct genetic alterations copy number variations among clusters, particularly which exhibited unique signatures. Immune infiltration showed that had higher expression levels immune checkpoint genes, stronger evasion activity, greater cell infiltration, suggesting an immunosuppressive tumor microenvironment. Furthermore, identified prognostic markers developed MITscore based on gene patterns, stratified patients high- low-risk groups. High groups displayed stemness characteristics, survival outcomes, differential responses to chemotherapy immunotherapy. Cross-validation drug sensitivity immunotherapy cohorts indicated high more sensitive certain chemotherapeutic agents responded better Finally, SRGA method, novel biomarkers (KDR, LRRK2, SQSTM1) closely mitochondrial function, may serve potential targets for therapeutic intervention. These findings highlight LGG prognosis, microenvironment regulation, treatment response, providing new avenues precision oncology.

Language: Английский

Citations

0
Pan-cancer association of a mitochondrial function score with genomic alterations and clinical outcome DOI Creative Commons

Shikun Zhu,

Chen Chen, Min Wang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 28, 2024

Mitochondria are pivotal in cellular energy metabolism and have garnered significant attention for their roles cancer progression therapy resistance. Despite this, the functional diversity of mitochondria across various types remains inadequately characterized. This study seeks to fill this knowledge gap by introducing validating MitoScore—a novel metric designed quantitatively assess mitochondrial function a wide array cancers. Our investigation evaluates capacity MitoScore not only distinguish between tumor adjacent normal tissues but also serve as predictive marker clinical outcomes. We analyzed gene expression data from 24 corresponding using TCGA database. was calculated summing normalized levels six genes known be consistently altered multiple Differential assessed DESeq2, with focus on identifying changes function. MitoScore's associations proliferation, hypoxia, aneuploidy, outcomes were evaluated Spearman's correlation, linear regression, Kaplan–Meier survival analyses. significantly higher compared most (p < 0.001). It positively correlated proliferation rates (r = 0.46), hypoxia scores 0.61), aneuploidy 0.44), indicating its potential aggressive behavior. High associated poorer prognosis several types, suggesting utility biomarker introduces MitoScore, activity often elevated tumors linked poor prognosis. correlates negatively stromal immune infiltration, highlighting mitochondria's role microenvironment. association genomic instability, such suggests dysfunction contributes progression. challenges mitochondrial-targeted therapies, may identify responsive treatments, warranting further research application.

Language: Английский

Citations

1
Comparison of Mitochondrial and Antineoplastic Effects of Amiodarone and Desethylamiodarone in MDA-MB-231 Cancer Line DOI Open Access
Fadi H. J. Ramadan, Balázs Kőszegi, Viola Bagóné Vántus

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9781 - 9781

Published: Sept. 10, 2024

Previously, we have demonstrated that amiodarone (AM), a widely used antiarrhythmic drug, and its major metabolite desethylamiodarone (DEA) both affect several mitochondrial processes in isolated heart liver mitochondria. Also, established DEA’s antitumor properties various cancer cell lines rodent metastasis model. In the present study, compared AM’s antineoplastic effects human triple-negative breast (TNBC) line. Both compounds reduced viability monolayer sphere cultures invasive growth of MDA-MB-231 TNBC line by inducing apoptosis. They lowered trans-membrane potential, increased Ca2+ influx, induced permeability transition, promoted fragmentation. accordance with their effects, substances massively decreased overall, even to greater extent, ATP production decreased, as determined using Seahorse live respirometer. all these DEA was more effective than AM, indicating may higher potential therapy parent compound.

Language: Английский

Citations

0
Multifaceted roles of mitochondria in asthma DOI Creative Commons
Wei Zhang, Chen‐Yu Zhang, Yi Zhang

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Oct. 9, 2024

Mitochondria are essential organelles within cells, playing various roles in numerous cellular processes, including differentiation, growth, apoptosis, energy conversion, metabolism, and immunity. The phenotypic variation of mitochondria is specific to different tissues cell types, resulting significant differences their function, morphology, molecular characteristics. Asthma a chronic, complex, heterogeneous airway disease influenced by external factors such as environmental pollutants allergen exposure, well internal at the tissue, cellular, genetic levels, lung structural immune granulocytes, mast cells. Therefore, comprehensive understanding responses stimuli changes crucial for elucidating pathogenesis asthma. Previous research on mitochondrial-targeted therapy asthma has primarily focused antioxidants. Consequently, it necessary summarize multifaceted discover additional strategies targeting this context. In review, our goal describe mitochondrial function response exposure across types other relevant context asthma, utilizing new terminology framework that encompasses cell-dependent characteristics, features, activity, behavior.

Language: Английский

Citations

0
CYP19A1 regulates chemoresistance in colorectal cancer through modulation of estrogen biosynthesis and mitochondrial function DOI Creative Commons
Yang Wang, Qiang Ji, N. Cao

et al.

Cancer & Metabolism, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 28, 2024

Abstract Chemoresistance remains a major challenge in the effective treatment of colorectal cancer (CRC), contributing to poor patient outcomes. While molecular mechanisms underlying chemoresistance are complex and multifaceted, emerging evidence suggests that altered mitochondrial function hormone signaling play crucial roles. In this study, we investigated role CYP19A1, key enzyme estrogen biosynthesis, regulating CRC. Using combination vitro functional assays, transcriptomic analysis, clinical data mining, demonstrate CYP19A1 expression is significantly upregulated CRC cells patient-derived samples compared normal controls. Mechanistically, found regulates through modulation I activity, which mediated by CYP19A1-dependent biosynthesis. Notably, targeted inhibition using specific inhibitors effectively reversed chemotherapeutic drugs. Moreover, analysis TCGA dataset revealed high correlates with overall survival chemotherapy-treated patients. Taken together, our findings uncover novel for signaling, highlight potential targeting CYP19A1/estrogen/complex axis as therapeutic strategy overcome improve

Language: Английский

Citations

0