Integrated Single‐Cell and Spatial Transcriptome Reveal Metabolic Gene SLC16A3 as a Key Regulator of Immune Suppression in Hepatocellular Carcinoma DOI Creative Commons

Qianlong Kang,

Xiaomeng Yin,

Zhenru Wu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

Hepatocellular carcinoma (HCC) is one of the most lethal cancers, usually diagnosed at an advanced stage. Metabolic reprogramming plays a significant role in HCC progression, probably related to immune evasion, yet key gene unclear. In this study, six metabolism-related genes with prognostic implications were screened. Correlation analysis between and cell subtypes was conducted, prominent strongly associated immunosuppression, SLC16A3, identified. Overexpression SLC16A3 loss T-cell function might lead upregulation several immunosuppressive proteins. Gene enrichment showed correlated primarily involved adhesion. Single-cell that mainly expressed macrophages, especially some tumour-promoting macrophages. Further spatial transcriptome data indicated enriched tumour invasion front. The mIHC revealed patients high expression exhibited significantly reduced infiltration GZMB

Language: Английский

Impact of glycolysis enzymes and metabolites in regulating DNA damage repair in tumorigenesis and therapy DOI Creative Commons

Fengyao Sun,

Wen Li,

Ruihang Du

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 23, 2025

Initially, it was believed that glycolysis and DNA damage repair (DDR) were two distinct biological processes independently regulate tumor progression. The former metabolic reprogramming rapidly generates energy generous intermediate metabolites, supporting the synthetic metabolism proliferation of cells. While DDR plays a pivotal role in preserving genomic stability, thus resisting cellular senescence cell death under both physiological radio-chemotherapy conditions. Recently, an increasing number studies have shown closely correlation between these processes, then promoting For instance, lactic acid, product glycolysis, maintains acidic microenvironment not only fosters invasion but also facilitates by enhancing AKT activity. Here, we provide comprehensive overview enzymes metabolites involved along with primary methods for DDR. Meanwhile, this review explores existing knowledge regulating Moreover, considering significant roles development resistance, present discusses effective direct or indirect therapeutic strategies targeted to

Language: Английский

Citations

3
Lactic acid: The culprit behind the immunosuppressive microenvironment in hepatocellular carcinoma DOI

Xiaopei Peng,

Zhenhu He,

Dandan Yuan

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189164 - 189164

Published: Aug. 2, 2024

Language: Английский

Citations

8
Metabolic gatekeepers: harnessing tumor-derived metabolites to optimize T cell-based immunotherapy efficacy in the tumor microenvironment DOI Creative Commons
Yucheng Zheng,

Rongwei Xu,

Xu Chen

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(10)

Published: Oct. 26, 2024

Language: Английский

Citations

7
Comprehensive pan-cancer analysis identified SLC16A3 as a potential prognostic and diagnostic biomarker DOI Creative Commons
Ping Yang,

Jiayu Yin,

Gongyin Zhang

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 29, 2025

Abstract SLC16A3, belonging to the SLC16 gene family, is involved in transportation of monocarboxylate. SLC16A family members play important roles tumorigenesis, nonetheless, specific involvement SLC16A3 tumor prognosis and diagnosis human cancers remains unelucidated. This study dealt with exploration expression pan-cancer its significance regarding disease prognosis. For this investigation, mRNA data were acquired from TCGA GTEx datasets. The Kaplan-Meier plots, univariate Cox regression, ROC curve employed for assessing prognostic diagnostic pan-cancer. Furthermore, cBioPortal database was used analyze genomic alterations. Moreover, association infiltration immune cells checkpoint genes analyzed by TIMER database. Gene Ontology KEGG pathway analysis explore function resulting demonstrated that overexpressed most protein also high across diverse cancer types. upregulated linked poor OS PFI certain cancers. regression further indicated a risk factor patients PAAD, CESC, LUSC, LUAD, CHOL, LGG, MESO, OSCC. revealed exhibited accuracy (AUC > 0.9) BRCA, ESCA, GBM, KIRC prediction. pan-cancer, correlations cells. These findings collectively suggest holds promise as biomarker purposes

Language: Английский

Citations

0
JTC801 regresses uveal melanoma progression through novel methuosis-like cell death via lysosomal dysfunction DOI Creative Commons
Qiuyan Liu,

Mingyan Huang,

Xinpei Ji

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Uveal melanoma (UM) is the most frequent primary intraocular malignancy in adults with high metastasis and mortality rate, whose effective therapeutic strategy still urgent need. Specifically, apoptosis-resistance a great challenge for advanced UM patients, therefore novel options targeting otherwise death modality, which may potentially enhance treatment effect, need to be further identified. Here, by kinase inhibitor library of 113 approved drugs screening, JTC801, selective antagonist nociceptin receptor (NOP), exhibits specifically strong tumor-killing ability lower dosage. JTC801 induces cell methuosis-like characterized cytoplasmic vacuolization, markedly regresses tumor progression metastasis, prolongs survival multiple models without apparent adverse effects. Mechanistically, JTC801-caused nutrient-deficient stress mitochondrial damage triggers macropinocytosis vacuolization cells. Concomitantly, trapped into macropinosomes that fuse lysosomes, causing lysosomal over-acidification, de-glycosylation associated membrane protein 1(LAMP1), inhibiting cathepsinsmaturation, exacerbating permeabilization (LMP), eventually inducing death. Collectively, our findings identify as potential valuable antitumor drug especially apoptosis-resistant provide insight distinct cytotoxicity role treatment.

Language: Английский

Citations

0
Osteopontin promotes tumor microenvironment remodeling and therapy resistance DOI
Chao Liu,

Shunjin Xia,

Wei Wang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217618 - 217618

Published: March 1, 2025

Language: Английский

Citations

0
NNMT promotes acquired EGFR-TKI resistance by forming EGR1 and lactate-mediated double positive feedback loops in non-small cell lung cancer DOI Creative Commons
Jiali Dai, Xiyi Lu, Chang Zhang

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 15, 2025

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are remarkably effective for treating EGFR-mutant non-small cell lung cancer (NSCLC). However, patients inevitably develop acquired drug resistance, resulting in recurrence or metastasis. It is important to identify novel therapeutic targets reverse TKI resistance. Bioinformatics analysis revealed that nicotinamide N-methyltransferase (NNMT) was upregulated EGFR-TKI resistant cells and tissues via EGR1-mediated transcriptional activation. High NNMT levels were correlated with poor prognosis EGFR-mutated NSCLC patients, which could promote resistance EGFR-TKIs vitro vivo. Mechanistically, catalyzed the conversion of 1-methyl by depleting S-adenosyl methionine (the methyl group donor), leading a reduction H3K9 trimethylation (H3K9me3) H3K27 (H3K27me3) subsequent epigenetic activation EGR1 ALDH3A1. In addition, ALDH3A1 increased lactic acid levels, further promoted expression p300-mediated histone H3K18 lactylation on its promoter. Thus, mediates formation double positive feedback loop lactate, EGR1/NNMT/EGR1 NNMT/ALDH3A1/lactate/NNMT. Moreover, combination small-molecule inhibitor (NNMTi) osimertinib exhibited promising potential treatment an osimertinib-resistant xenograft model. The combined contribution these two loops promotes NSCLC. Our findings provide new insight into role methylation pivotal NNMT-mediated may serve as powerful target overcoming

Language: Английский

Citations

0
The Intersections between Neuroscience and Medulloblastoma DOI
Yafei Wang, Ying Yu, Jiahua Yu

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217660 - 217660

Published: March 1, 2025

Language: Английский

Citations

0
Intersection between lung cancer and neuroscience: opportunities and challenges DOI
Xiang Xiao, Lingli Huang, Ming Li

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217701 - 217701

Published: April 1, 2025

Language: Английский

Citations

0
Pan-cancer analysis reveals BAF complexes as immune-related biomarkers and validation in triple-negative breast cancer DOI
Shuying Dai, Bei Li, Qingqian Wu

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123607 - 123607

Published: April 1, 2025

Language: Английский

Citations

0