RNA expression data suggest ALDH2 inhibition as a concept for killing acute myeloid leukemia cells that are resistant to ALDH1 inhibitors: the example of NPM1 mutant AML DOI Creative Commons
Garrett M. Dancik, Spiros Vlahopoulos

Опубликована: Ноя. 10, 2024

Abstract In this data paper we present a study of RNA expression in association with the disease course acute myeloid leukemia (AML). We have previously identified aldehyde dehydrogenase genes ALDH1A1 and ALDH2 as prospective actionable targets AML. is expected to key functions stem-like cells that are prone dormant state terms metabolic activity proliferation. Cells higher metabolism whole mitochondria particular, likely generate abundance formaldehyde acetaldehyde. Cell survival necessitates removal acetaldehyde, which substantial degree function ALDH2. AML mutant NPM1 gene permit MYC would lead increased activity. Extended allowed by protein, compared wild-type. Here, show analysis patients yields hazard ratio for than , not case wild-type NPM1. This result consistent difference enzymatic between ALDH1A1, latter suited small aldehydes, especially formaldehyde. should open door examination inhibitors such clinically approved disulfiram, treatment proves refractory inhibition.

Язык: Английский

Metabolic regulation of the immune system in health and diseases: mechanisms and interventions DOI Creative Commons
Tengyue Hu, Changhai Liu, Min Lei

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Язык: Английский

Процитировано

26
Transcriptional regulation and post-translational modifications in the glycolytic pathway for targeted cancer therapy DOI
Xuan Ni,

Chengpiao Lu,

Guo-qiang Xu

и другие.

Acta Pharmacologica Sinica, Год журнала: 2024, Номер 45(8), С. 1533 - 1555

Опубликована: Апрель 15, 2024

Язык: Английский

Процитировано

11
MYC: there is more to it than cancer DOI Creative Commons
Mariano F. Zacarías Fluck, Laura Soucek, Jonathan R. Whitfield

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 6, 2024

MYC is a pleiotropic transcription factor involved in multiple cellular processes. While its mechanism of action and targets are not completely elucidated, it has fundamental role proliferation, differentiation, metabolism, ribogenesis, bone vascular development. Over 4 decades research some 10,000 publications linking to tumorigenesis (by searching PubMed for “MYC oncogene”) have led becoming most-wanted target the treatment cancer, where many MYC’s physiological functions become co-opted tumour initiation maintenance. In this context, an abundance reviews describes strategies potentially targeting oncology field. However, roles different aspects biology suggest that may also play additional diseases, other indeed pathologies beyond cancer. Here, we review these current literature non-oncological diseases. The intense efforts towards developing inhibitors as cancer therapy will huge implications addition, with complementary approach, discuss diseases conditions appears protective hence increased expression or activation could be therapeutic.

Язык: Английский

Процитировано

9
CXCR4 regulates macrophage M1 polarization by altering glycolysis to promote prostate fibrosis DOI Creative Commons
Yi Zhang, Chen Zhang, Rui Feng

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 26, 2024

Язык: Английский

Процитировано

4
Infectious Spleen and Kidney Necrosis Virus ORF093R and ORF102R Regulate Glutamate Metabolic Reprogramming to Support Virus Proliferation by Interacting with c-Myc DOI Open Access
Yinjie Niu,

Caimei Ye,

Qiang Lin

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 718 - 718

Опубликована: Янв. 16, 2025

Glutamine metabolism is essential for infectious spleen and kidney necrosis virus (ISKNV) replication. Glutaminase 1 (GLS1), the key enzyme of glutamine metabolism, c-Myc positively regulate ISKNV infection, while closely correlated with GLS1. However, regulatory mechanism among ISKNV, remains unclear. Here, we indicated that increased uptake by increasing GLS1, glutamate dehydrogenase (GDH) isocitrate (IDH2) expression metabolism. ORF102R, ORF093R ORF118L co-located in CPB cells. Co-IP results showed ORF102R interacted c-Myc, did not interact c-Myc. The levels GLS1 IDH2 were cells, mRNA protein upregulated 102R-expressing These reconstructed to satisfy energy macromolecule requirements proliferation interacting which provides foundation innovative antiviral strategies.

Язык: Английский

Процитировано

0
Eugenol Promotes Apoptosis in Leukemia Cells via Targeting the Mitochondrial Biogenesis PPRC1 Gene DOI Creative Commons

Sayer Al-harbi,

Elham M. A. Alkholiwy,

Syed Osman Ali Ahmed

и другие.

Cells, Год журнала: 2025, Номер 14(4), С. 260 - 260

Опубликована: Фев. 12, 2025

Acute myeloid leukemia (AML) is a highly heterogenous and aggressive neoplasm. To sustain growth survival, AML cells, like other neoplasms, require energy. This process orchestrated by mitochondria under the control of several genes, such as PPRC1 (PRC), member PGC-1 family, which key player in transcription mitochondrial biogenesis. We have shown here that eugenol inhibits cell promotes apoptosis through pathway lines well cells from patients but not healthy donors. Similar effects were also observed on cytarabine-resistant cells. Interestingly, downregulated at both protein mRNA levels reduced membrane potential expression higher cancer blood, breast, types relative to normal high correlate significantly with short overall survival (OS). In addition, gene mutations OS and/or disease-free cancers. correlated poor (p < 0.0001) when tested total 23,456 patients. These findings suggest an oncogenic role various possible eugenol-targeting this for treatment patients, especially those exhibiting resistance cytarabine.

Язык: Английский

Процитировано

0
Effective Herbal Cocktail Strategies and Mechanisms in Cancer Treatment DOI Creative Commons
Tian He, Yifan Zhang, Di Deng

и другие.

Integrative Cancer Therapies, Год журнала: 2025, Номер 24

Опубликована: Янв. 1, 2025

Systematic treatment and cocktailed drug applications have become a paradigm shift for cancer therapy. This study aims to explore the highly potent herbal cocktail strategies pharmacological mechanisms, by which medicines are effective in treatment. A total of 397 cases clinically reported treatments with pure herbs were scrutinized, prescription rules systematically analyzed. The core prescriptions their mechanisms revealed. results unveiled specific cancer, including boosting energy metabolism, inhibiting tumor proliferation, improving digestion defecation, enhancing blood circulation, promoting gas exchange, facilitating water toxic substance metabolism. Pharmacologically, anti-cancer effects achieved through manipulation PI3K-Akt, IL-17, HIF-1, VEGF, TNF, Wnt, other pathways. Following this unfolded integrative rule, therapy demonstrated remarkable clinical practices, from few representative presented herein.

Язык: Английский

Процитировано

0
Trichostatin A augments cell migration and epithelial-mesenchymal transition in esophageal squamous cell carcinoma through BRD4/c-Myc endoplasmic reticulum-stress pathway DOI

Yanmin Chen,

Wenqian Yang, Yingying Fan

и другие.

World Journal of Gastroenterology, Год журнала: 2025, Номер 31(11)

Опубликована: Март 12, 2025

BACKGROUND The causes of death in patients with advanced esophageal cancer are multifactorial, tumor metastasis being one the important factors. Histone acetylation promotes migration squamous cell carcinoma (ESCC) cells, while histone deacetylase inhibitor (HDACi) shows complex effects on functions. AIM To comprehensively elucidate impact and molecular mechanisms trichostatin A (TSA), an HDACi, ESCC through bromodomain-containing protein (BRD4)/cellular myelocytomatosis oncogene (c-Myc)/endoplasmic reticulum (ER)-stress. METHODS TSA lines Eca109 EC9706 were evaluated using Transwell assays, small interfering transfection pathway-specific inhibitors to underlying mechanisms. mRNA levels involved examined by quantitative real-time polymerase chain reaction. Protein acetylated histones H3 (acH3) H4, BRD4, c-Myc, as well markers ER stress epithelial-mesenchymal transition (EMT), analyzed western blot. Additionally, this method was also used examine acH3 tissues adjacent tissues. Patient outcomes subsequently tracked identify prognostic indicators Log-Rank tests Cox multivariate analysis. RESULTS promoted cells stimulating EMT process. TSA-mediated facilitated recruitment a protein, triggering expression c-Myc. This cascade induced enhanced cells. further mechanism, we employed various interventions including 4-phenylbutyric acid, knockdown c-Myc BRD4 expression, utilization carboxylic acid 1. Mechanistically, these studies revealed that which turn triggered sequential activation EMT, thereby promoting specimens from 43 ESCC, both paired Statistical analysis unveiled negative correlation between level long-term prognosis ESCC. CONCLUSION BRD4/c-Myc/ER pathway. Moreover, elevated correlated poor prognosis. These findings enhance our understanding HDACi therapy.

Язык: Английский

Процитировано

0
Stathmin 1 regulates mitophagy and cellular function in hematopoietic stem cells DOI Open Access

Luana Chiquetto,

Michael Schuetz, Dong Qian

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Stathmin 1 is a cytoplasmic phosphoprotein that regulates microtubule dynamics via promotion of catastrophe and sequestration free tubulin heterodimers. highly expressed in hematopoietic stem cells (HSCs), overexpressed leukemic cells, however its role HSCs not known. Herein, we found loss associated with altered architecture HSCs, markedly impaired HSC function. Transcriptomic studies suggested alterations oxidative phosphorylation Stmn1 -/- further mechanistic revealed defective mitochondrial structure function the absence increased ROS production. Microtubules associate mitochondria lysosomes to facilitate autophagosome formation mitophagy, indeed this critical quality control process 1-deficient HSCs. Finally, stimulation autophagy improved colony forming ability progenitor cells. Together, our data identify as novel regulator mitophagy health The regulating protein HSPCs promotes normal architecture.Loss leads abnormal morphology, decreased respiratory capacity, cellular

Язык: Английский

Процитировано

0
PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity DOI Open Access

Grigor Varuzhanyan,

Chia‐Chun Chen, Jack Freeland

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 13, 2024

ABSTRACT Adenocarcinomas from multiple tissues can evolve into lethal, treatment-resistant small cell neuroendocrine (SCN) cancers comprising subtypes with poorly defined metabolic characteristics. The role of metabolism in directly driving subtype determination remains unclear. Through bioinformatics analyses thousands patient tumors, we identified enhanced PGC-1α—a potent regulator oxidative phosphorylation (OXPHOS)—in various SCN (SCNCs), closely linked differentiation. In a patient-derived prostate tissue SCNC transformation system, the ASCL1-expressing showed elevated PGC-1α expression and increased OXPHOS activity. Inhibition reduced proliferation lung cancer lines blocked tumor formation. Conversely, enhancing PGC- 1α OXPHOS, validated by small-animal Positron Emission Tomography mitochondrial imaging, tripled formation rate promoted commitment to ASCL1 lineage. These results establish as driver progression determination, highlighting novel vulnerabilities SCNCs across different tissues. STATEMENT OF SIGNIFICANCE Our study provides functional evidence that reprogramming impact phenotypes establishes PGC-1α-induced lineage determination. mechanistic insights reveal common originating tissues, opening new avenues for pan-SCN therapeutic strategies.

Язык: Английский

Процитировано

3