SLC25A19 is a novel prognostic biomarker related to immune invasion and ferroptosis in HCC DOI Creative Commons
Shiqi Liu, Pengjie Zhang, Yubo Wu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 136, P. 112367 - 112367

Published: May 31, 2024

SLC25A19 is a mitochondrial thiamine pyrophosphate (TPP) carrier that mediates TPP entry into the mitochondria. has been recognized to play crucial role in many metabolic diseases, but its cancer not clearly reported. Based on clinical data from The Cancer Genome Atlas (TCGA), following parameters were analyzed among HCC patients: expression, enrichment analyses, immune infiltration, ferroptosis and prognosis analyses. In vitro, high expression was validated by qRT-PCR Immunohistochemistry. Subsequently, series of cell function experiments, including CCK8, EdU, clone formation, trans-well scratch assays, conducted illustrate effect growth metastasis cells. Meanwhile, indicators related also detected. SCL25A19 highly expressed predicts poor prognosis. Elevated patients markedly associated with T stage, pathological status (PS), tumor (TS), histologic grade (HG), AFP. Our results indicate generally good predictive diagnostic ability. gene analyses showed significantly correlated fatty acid metabolism, marker genes. vitro experiments have confirmed silencing can inhibit proliferation migration ability cells induce HCC. conclusion, these findings novel prognostic biomarker invasion HCC, it an excellent candidate for therapeutic target against

Language: Английский

The diversified role of mitochondria in ferroptosis in cancer DOI Creative Commons
Yue Liu,

Shi-Ping Lu,

Lei‐Lei Wu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(8)

Published: Aug. 14, 2023

Abstract Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced iron overload ROS accumulation, ferroptosis modulated various cellular metabolic signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 GCH1-BH4 DHODH-CoQH2 system sex hormones suppress ferroptosis. Mitochondrial metabolism regulates mitochondria also undergo morphological change during ferroptosis, these changes include increased membrane density reduced mitochondrial cristae. Moreover, energy oxidative phosphorylation ATP production rates lead to decrease glycolysis rate. In addition, excessive stress induces irreversible damage mitochondria, diminishing organelle integrity. production, potential, fusion fission, mitophagy function Notably, some inhibitors target mitochondria. major mechanism for associated with progression cancer. Metastasis-prone or metastatic cancer cells are more susceptible Inducing tumor shows very promising potential treating drug-resistant cancers. this review, we present brief retrospect characteristics then discuss regulation highlight unique role played cells. Furthermore, explain how functions as double-edged sword well novel therapies aimed at selectively manipulating eradication.

Language: Английский

Citations

149
Role of mitochondrial alterations in human cancer progression and cancer immunity DOI Creative Commons
Sheng‐Fan Wang, Ling‐Ming Tseng, Hsin‐Chen Lee

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: July 31, 2023

Abstract Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, metabolism, apoptosis, and calcium redox homeostasis. Although “Warburg effect,” in which cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to progression still unclear. This review discusses recent progress alterations DNA (mtDNA) dynamics malignant progression. Moreover, we integrate possible regulatory mechanism dysfunction–mediated retrograde signaling pathways, including mitochondrion-derived molecules (reactive species, calcium, oncometabolites, mtDNA) stress response pathways (mitochondrial unfolded protein integrated response) provide therapeutic targets. Furthermore, discuss findings on role mitochondria immune function reveal impact tumor microenvironment remodeling immunity. Targeting might improve immunotherapy. These suggest that targeting malignancy modulating immunity be promising treatment strategies patients precise personalized medicine against cancer.

Language: Английский

Citations

61
Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization DOI Creative Commons

Chier Du,

Xun Guo,

Xiaoling Qiu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 11, 2024

Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature damage‐repair capabilities malignant tumors strongly limit efficacy treatments based on a single treatment mode. To address this challenge, self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) calcium peroxide (CaO 2 ) into hyaluronic (HA) ‐modified metal‐organic frameworks (MOF). After cellular, dissociates CaO Cu 2+ tumor microenvironment. The exposed further yields hydrogen (H O Ca weakly acidic environment to strengthen ‐based Fenton‐like reaction. Furthermore, combination chemodynamic therapy overload exacerbates ROS storms mitochondrial damage, resulting downregulation intracellular adenosine triphosphate (ATP) levels blocking Cu‐ATPase sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic death suppresses metastasis simultaneously. study presents multivariate model for revolutionizing mitochondria relying continuous retention ions boost cuproptosis/immunotherapy cancer.

Language: Английский

Citations

33
Prognostic relevance and validation of ARPC1A in the progression of low-grade glioma DOI Creative Commons

Jingyuan Dai,

Jiahui Gao, Hongchao Dong

et al.

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: June 19, 2024

Low-grade glioma (LGG) is a grade II-III accompanied by distinct clinical and molecular characteristics the studies related to its prognosis are still unclear. The objective of this study explore involvement mitochondrial-related genes SLBP, COMMD7, LSM4, TOMM34, RPP40, FKBP1A, ARPC1A, TBCA for LGG. We detected differences in expression some analyzing bioinformatics dataset combining it with RT-PCR experiments. Subsequently, nomogram was constructed validated relevance risk factors such as age, WHO grade, IDH mutation status, Ch.1p19q co-deletion high low ARPC1A predict 1-, 3-, 5-year overall survival prognostic ARPC1A. Gene set enrichment analysis performed relevant datasets pertinent elucidate cancer-promoting pathways involved LGG through KEGG GO analysis. Transfection assays, CCK-8 flow cytometry were used determine proliferation rate, apoptosis rate HS683 SW1783 cell lines respectively. Western blotting examine activity MAPK signaling. In study, value found combined experimental approach may be significant independent factor. fosters higher that control MAP kinase signaling could prominent biomarker Future warranted implications.

Language: Английский

Citations

19
Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection DOI

Xutong Qiu,

Yi Li,

Zhuoyuan Zhang

et al.

Cellular Oncology, Journal Year: 2023, Volume and Issue: 46(4), P. 847 - 865

Published: April 11, 2023

Language: Английский

Citations

28
Exploring the mystery of tumor metabolism: Warburg effect and mitochondrial metabolism fighting side by side DOI
Yongxin Yu,

Yulang Jiang,

Christian Glandorff

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 120, P. 111239 - 111239

Published: May 28, 2024

Language: Английский

Citations

13
Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy DOI
Bo‐Xin Zheng,

Wei Long,

Wende Zheng

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6292 - 6312

Published: April 16, 2024

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) emerging small molecules. Despite some mitochondria-selective ligands being reported delivery against cancers, the ligand design is mostly limited to triphenylphosphonium scaffold. The designed with lipophilic small-sized scaffolds bearing multipositive charges targeting unique feature high membrane potential (MMP) lacking most not G4-targeting. Herein, we report a new dicationic target MMP G4s enhance anticancer. showed marked alteration gene expression substantial induction ROS production, dysfunction, damage, cellular senescence, apoptosis. also exhibited activity HCT116 cancer cells (IC50, 3.4 μM) antitumor efficacy in tumor xenograft mouse model (∼70% weight reduction).

Language: Английский

Citations

10
Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages DOI Creative Commons

Shian Hu,

Zehua Yang, Ling Li

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(1), P. 236 - 236

Published: Jan. 1, 2024

Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from roots of Salvia miltiorrhiza Bunge. This research was designed to reveal potential mechanism Sal anti-liver injury perspective macrophages. In our lipopolysaccharide-induced M1 macrophage model, showed a clear dose-dependent gradient inhibition trend type. Moreover, downregulated expression lactate dehydrogenase A (LDHA), while overexpression LDHA impaired B’s effect inhibiting polarization. Additionally, this study revealed that exhibited inhibitory effects on lactylation process histone H3 lysine 18 (H3K18la). ChIP-qPCR analysis, observed drive reduction in H3K18la levels promoter region LDHA, NLRP3, and IL-1β genes. Furthermore, vivo experiments has good alleviating CCl4-induced liver injury. An examination tissues Kupffer cells isolated those proved affects polarization macrophages level lactylation. Together, data by downregulating treatment

Language: Английский

Citations

9
New Insights into Mitochondria in Health and Diseases DOI Open Access
Ya Li, Huhu Zhang,

Chunjuan Yu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9975 - 9975

Published: Sept. 16, 2024

Mitochondria are a unique type of semi-autonomous organelle within the cell that carry out essential functions crucial for cell's survival and well-being. They location where eukaryotic cells energy metabolism. Aside from producing majority ATP through oxidative phosphorylation, which provides cellular functions, mitochondria also participate in other metabolic processes cell, such as electron transport chain, citric acid cycle, β-oxidation fatty acids. Furthermore, regulate production elimination ROS, synthesis nucleotides amino acids, balance calcium ions, process death. Therefore, it is widely accepted mitochondrial dysfunction factor causes or contributes to development advancement various diseases. These include common systemic diseases, aging, diabetes, Parkinson's disease, cancer, well rare disorders, like Kearns-Sayre syndrome, Leigh myopathy. This overview outlines mechanisms by involved numerous illnesses physiological activities. Additionally, new discoveries regarding involvement both disorders maintenance good health.

Language: Английский

Citations

9
Relevance of Cardiovascular Exercise in Cancer and Cancer Therapy-Related Cardiac Dysfunction DOI Creative Commons
Simon Wernhart, Tienush Rassaf

Current Heart Failure Reports, Journal Year: 2024, Volume and Issue: 21(3), P. 238 - 251

Published: May 2, 2024

Abstract Purpose of the Review Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) shown improve cardiorespiratory fitness (CRF), relationship between specific regimens cancer survival, heart failure development, reduction CTRCD is unclear. In this review, we discuss impact AET on molecular pathways current literature sports in field cardio-oncology. Recent Findings Cardio-oncological trials have focused variations intensity by using moderate continuous high interval training, which are applicable, safe, effective approaches CRF. Summary increases CRF, reduces cardiovascular morbidity hospitalization should thus be implemented an adjunct standard therapy, although its long-term effect remains unknown. Despite modulating diverse pathways, it unknown regimen, including duration frequency, most suited facilitate peripheral central adaptations survival patients.

Language: Английский

Citations

8