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

A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments DOI Creative Commons
Christopher Chidley, Alicia M. Darnell, Benjamin L. Gaudio

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(5), P. 825 - 838

Published: April 11, 2024

Abstract Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report CRISPR interference/activation screening platform systematically interrogate contribution nutrient support in environments ranging from standard culture media tumours. We applied this identify amino acids leukaemia cells and found that acid transport involves high bidirectional flux dependent on microenvironment composition. While investigating role cystine starved cells, uncovered serotonin uptake preventing ferroptosis. Finally, identified subcutaneous tumours levels glucose can restrain environment. This study establishes framework identifying critical cellular transporters, characterizing their function exploring how tumour impacts metabolism.

Language: Английский

Citations

14
Genotype × environment interactions in gene regulation and complex traits DOI
Carly Boye, Shreya Nirmalan, Ali Ranjbaran

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Language: Английский

Citations

14
The redox requirement and regulation during cell proliferation DOI
Z P. Zhen, Jiankun Ren, Jiajun Zhu

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(5), P. 385 - 399

Published: Jan. 22, 2024

Language: Английский

Citations

11
Iron metabolism disorder and multiple sclerosis: a comprehensive analysis DOI Creative Commons
Chao Tang, Jiaxin Yang,

Chaomin Zhu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 21, 2024

Background Multiple sclerosis (MS) is the most common chronic inflammatory disease of central nervous system. Currently, pathological mechanisms MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with onset and clinical manifestations MS. Methods materials The study utilized publicly available databases bioinformatics techniques for gene expression data analysis, including differential weighted correlation network enrichment construction logistic regression models. Subsequently, Mendelian randomization was used to assess causal relationship between different markers Results This identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, SKP1 as genes multiple metabolism, establishing their multi-gene diagnostic value an AUC 0.83. Additionally, analysis revealed a potential transferrin saturation (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), well serum (p=2.18E-04; 95%CI=1.22 (1.10, 1.36)). Conclusion comprehensively explored through integrated methods. findings provide important insights further into role in pathogenesis offer crucial theoretical support treatment

Language: Английский

Citations

11
Multimodal AI/ML for discovering novel biomarkers and predicting disease using multi-omics profiles of patients with cardiovascular diseases DOI Creative Commons

William DeGroat,

Habiba Abdelhalim,

Elizabeth Peker

et al.

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

Published: Nov. 3, 2024

Cardiovascular diseases (CVDs) are complex, multifactorial conditions that require personalized assessment and treatment. Advancements in multi-omics technologies, namely RNA sequencing whole-genome sequencing, have provided translational researchers with a comprehensive view of the human genome. The efficient synthesis analysis this data through integrated approach characterizes genetic variants alongside expression patterns linked to emerging phenotypes, can reveal novel biomarkers enable segmentation patient populations based on risk factors. In study, we present cutting-edge methodology rooted integration traditional bioinformatics, classical statistics, multimodal machine learning techniques. Our has potential uncover intricate mechanisms underlying CVD, enabling patient-specific response profiling. We sourced transcriptomic single nucleotide polymorphisms (SNPs) from both CVD patients healthy controls. By integrating these datasets clinical demographic information, generated profiles. Utilizing robust feature selection approach, identified signature 27 features SNPs effective predictors CVD. Differential analysis, combined minimum redundancy maximum relevance selection, highlighted explain disease phenotype. This prioritizes biological efficiency learning. employed Combination Annotation Dependent Depletion scores allele frequencies identify pathogenic characteristics patients. Classification models trained demonstrated high-accuracy predictions for best performing was an XGBoost classifier optimized via Bayesian hyperparameter tuning, which able correctly classify all our test dataset. Using SHapley Additive exPlanations, created assessments patients, offering further contextualization setting. Across cohort, RPL36AP37 HBA1 were scored as most important predicting CVDs. A literature review revealed substantial portion diagnostic previously been associated framework propose study is unbiased generalizable other disorders.

Language: Английский

Citations

10
Solute carriers: The gatekeepers of metabolism DOI
Artem Khan, Yuyang Liu, Mark Gad

et al.

Cell, Journal Year: 2025, Volume and Issue: 188(4), P. 869 - 884

Published: Feb. 1, 2025

Language: Английский

Citations

1
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion DOI Creative Commons
Laura Onuchic, Valeria Padovano, Giorgia Schena

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 30, 2023

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent potentially lethal monogenic disorder. Mutations in PKD1 gene, which encodes polycystin-1 (PC1), account for approximately 78% of cases. PC1 a large 462-kDa protein that undergoes cleavage its N and C-terminal domains. produces fragments translocate to mitochondria. We show transgenic expression corresponding final 200 amino acid (aa) residues two Pkd1 -KO orthologous murine models ADPKD suppresses cystic phenotype preserves renal function. This suppression depends upon an interaction between tail mitochondrial enzyme Nicotinamide Nucleotide Transhydrogenase (NNT). modulates tubular/cyst cell proliferation, metabolic profile, function, redox state. Together, these results suggest short fragment sufficient suppress open door exploration gene therapy strategies ADPKD.

Language: Английский

Citations

21
Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis DOI Creative Commons
Xiaojian Shi,

Marisa DeCiucis,

Kariona A. Grabińska

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 84(4), P. 802 - 810.e6

Published: Dec. 28, 2023

Language: Английский

Citations

20
Nutrient transporters: connecting cancer metabolism to therapeutic opportunities DOI
Zeribe C. Nwosu,

Mun Gu Song,

Marina Pasca di Magliano

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(10), P. 711 - 724

Published: Feb. 4, 2023

Language: Английский

Citations

19
Macroautophagy/autophagy promotes resistance to KRASG12D-targeted therapy through glutathione synthesis DOI Creative Commons
Leng Han,

Lingjun Meng,

Jiao Liu

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 604, P. 217258 - 217258

Published: Sept. 13, 2024

Language: Английский

Citations

6