Prognostic iron-metabolism signature robustly stratifies single-cell characteristics of hepatocellular carcinoma DOI Creative Commons
Zhipeng Zhu, Cao Huang, Hongyu Yan

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 929 - 941

Published: Feb. 1, 2024

Cancer immunotherapy has shown to be a promising method in treating hepatocellular carcinoma (HCC), but suboptimal responses patients are attributed the cellular and molecular heterogeneity. Iron metabolism-related genes (IRGs) important maintaining immune system homeostasis have potential help developed new strategies for HCC treatment. Herein, we constructed validated iron-metabolism gene prognostic index (IPX) using univariate cox proportional hazards regression LASSO analysis, successfully categorizing into two groups with distinct survival risk. Then, performed single-sample set enrichment weighted correlation network ontology lineage analysis SCENIC reveal key determinants underlying ability of this model based on bulk single-cell transcriptomic data. We identified several driver transcription factors specifically activated specific malignant cell sub-populations contribute adverse outcomes IPX-high subgroup. Within tumor microenvironment (TME), T cells displayed significant diversity their characteristics experienced changes developmental paths within clusters by IPX. Interestingly, proportion Treg was increased high-risk group compared low-risk group. These results suggest that could involved reshaping TME, thereby disrupting cycle cells. This study utilized IRGs construct novel reliable model, which can used assessing prognosis further clarified mechanisms at resolution.

Language: Английский

ROS‐Responsive Injectable Hydrogel Loaded with SLC7A11‐modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats DOI

Tian Gao,

Guangyu Xu, Tiancong Ma

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(27)

Published: May 1, 2024

Abstract Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, pain imposes significant global economic burden. However, effectiveness treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective by focusing on as starting point. In study, an injectable reactive oxygen species‐responsive hydrogel (PVA‐tsPBA@SLC7A11 modRNA) developed, designed achieve rapid loading selective release chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA specifically used upregulate expression ferroptosis marker SLC7A11. The local injection PVA‐tsPBA@SLC7A11 into degenerated intervertebral (IVD) results in cleavage PVA‐tsPBA, leading enclosed modRNA. extent directly proportional severity IVDD, ultimately ameliorating inhibiting nucleus pulposus cells (NPCs). This proposes system PVA‐tsPBA hydrogel‐encapsulated modRNA, representing potential novel treatment strategy patients early‐stage IVDD.

Language: Английский

Citations

9
SLC7A11: the Achilles heel of tumor? DOI Creative Commons

Yulang Jiang,

Mingyu Sun

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

Published: July 8, 2024

The non-natriuretic-dependent glutamate/cystine inverse transporter-system Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with serving as the primary functional component responsible for cystine uptake glutathione biosynthesis. implicated in tumor development through its regulation redox homeostasis, amino acid metabolism, modulation immune function, induction programmed cell death, among other processes relevant to tumorigenesis. In this paper, we summarize structure biological functions SLC7A11, discuss potential role therapy, which provides a new direction precision personalized treatment tumors.

Language: Английский

Citations

9
LINC01088 prevents ferroptosis in glioblastoma by enhancing SLC7A11 via HLTF/USP7 axis DOI Creative Commons
Yujie Zhou,

Zhen Zhao,

Jiang Cheng

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Glioblastoma multiforme (GBM)is a highly aggressive malignancy of the central nervous system characterized by poor survival rates. Ferroptosis, an iron-dependent cell death pathway, is promising therapeutic target for GBM. However, current treatments targeting pathways have not yielded expected results. Long noncoding RNAs (lncRNAs) been implicated in tumour proliferation, however, their role ferroptosis GBM remains underexplored. This study investigated interplay between lncRNA LINC01088 and to identify novel strategies. We conducted gain- loss-of-function studies assess impact on tumourigenesis both vitro vivo. Bioinformatics, dual-luciferase reporter assays, chromatin immunoprecipitation, RNA pulldown, mass spectrometry, immunoprecipitation (RIP), transcriptome sequencing were utilized elucidate mechanisms underlying expression its downstream effects ferroptosis. The transcription factor specificity protein 1 (SP1) was identified as promoter transcription, which facilitated progression. found inhibit promote malignancy. Mechanistically, stabilized HLTF enhancing interaction with USP7 preventing ubiquitin-mediated degradation. stabilization led upregulation SLC7A11, inhibits Rescue experiments confirmed that altering levels reversed ferroptotic phenotypes associated modulation. revealed SP1/LINC01088/HLTF/USP7/SLC7A11 axis regulates GBM, highlighting potential ferroptosis-dependent treatment. transcriptionally upregulated SP1. acts scaffold platform bind HLTF. USP7, deubiquitinating enzyme HLTF, participates inhibiting ubiquitin-proteasome degradation upregates cells inhibited.

Language: Английский

Citations

1
Identification of SLC7A11‐AS1/SLC7A11 pair as a ferroptosis‐related therapeutic target for hepatocellular carcinoma DOI Creative Commons
Xiao Yuan, Yida Wang,

Sitong Jiao

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(13)

Published: July 1, 2024

Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as novel approach for HCC complexities. Moreover, while the interaction between long non-coding RNAs (lncRNAs) and mRNAs is pivotal various physiological pathological processes, their involvement ferroptosis remains relatively unexplored. In this study, we constructed ferroptosis-related lncRNA-mRNA correlation network using Pearson analysis. Notably, SLC7A11-AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed expression levels pair key clinical characteristics patients, including gender, pathology, Ishak scores tumour size. And poor prognosis associated with pair. Functional experiments demonstrated that SLC7A11-AS1, by binding to 3'UTR region SLC7A11 mRNA, enhanced its stability, thereby promoting cell growth resistance erastin- induced ferroptosis. Additionally, vivo studies confirmed SLC7A11-AS1 knockdown potentiated inhibitory effects erastin on growth. Overall, our findings suggest targeting holds potential strategy patients.

Language: Английский

Citations

6
Disulfidptosis: a novel cell death modality induced by actin cytoskeleton collapse and a promising target for cancer therapeutics DOI Creative Commons
Tianyi Li, Ying Song, Lijuan Wei

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 11, 2024

Disulfidptosis is a novel discovered form of programmed cell death (PCD) that diverges from apoptosis, necroptosis, ferroptosis, and cuproptosis, stemming disulfide stress-induced cytoskeletal collapse. In cancer cells exhibiting heightened expression the solute carrier family 7 member 11 (SLC7A11), excessive cystine importation reduction will deplete nicotinamide adenine dinucleotide phosphate (NADPH) under glucose deprivation, followed by an increase in intracellular stress aberrant bond formation within actin networks, ultimately culminating collapse disulfidptosis. involves crucial physiological processes eukaryotic cells, such as uptake, NADPH metabolism, dynamics. The Rac1-WRC pathway-mediated polymerization also implicated this due to its contribution formation. However, precise mechanisms underlying disulfidptosis role tumors are not well understood. This probably multifaceted functionalities SLC7A11 complexities downstream pathways driving review describes critical roles summarizes recent research advancements potential Moreover, less-studied aspects newly process highlighted stimulate further investigations field.

Language: Английский

Citations

6
Disulfidptosis-related signature elucidates the prognostic, immunologic, and therapeutic characteristics in ovarian cancer DOI Creative Commons

Yunyan Cong,

Guangyao Cai,

Chengcheng Ding

et al.

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

Published: April 17, 2024

Ovarian cancer (OC) is the deadliest malignancy in gynecology, but mechanism of its initiation and progression poorly elucidated. Disulfidptosis a novel discovered type regulatory cell death. This study aimed to develop disulfidptosis-related prognostic signature (DRPS) for OC explore effects potential treatment by risk stratification.

Language: Английский

Citations

5
Epigenetic modulation of ferroptosis in cancer: Identifying epigenetic targets for novel anticancer therapy DOI
Jaewang Lee, Jong‐Lyel Roh

Cellular Oncology, Journal Year: 2023, Volume and Issue: 46(6), P. 1605 - 1623

Published: July 12, 2023

Language: Английский

Citations

12
Ferroptosis: a critical mechanism of N6-methyladenosine modification involved in carcinogenesis and tumor progression DOI
Qingqing Wei,

Changning Xue,

Mengna Li

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: 67(6), P. 1119 - 1132

Published: Feb. 28, 2024

Language: Английский

Citations

4
Decoding the Role of O-GlcNAcylation in Hepatocellular Carcinoma DOI Creative Commons
Xinyu Zhou,

Sirui Hang,

Qingqing Wang

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 908 - 908

Published: July 25, 2024

Post-translational modifications (PTMs) influence protein functionality by modulating stability, localization, and interactions with other molecules, thereby controlling various cellular processes. Common PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, SUMOylation, methylation, sulfation, nitrosylation. Among these modifications, O-GlcNAcylation has been shown to play a critical role in cancer development progression, especially hepatocellular carcinoma (HCC). This review outlines the of progression HCC. Moreover, we delve into underlying mechanisms HCC highlight compounds that target O-GlcNAc transferase (OGT) O-GlcNAcase (OGA) improve treatment outcomes. Understanding will offer insights potential therapeutic strategies targeting OGT OGA, which could for patients

Language: Английский

Citations

4
New Insights into Reductive Stress Responses and its Clinical Relation in Cancer DOI
Suman Kumar Ray, Sukhes Mukherjee

Tissue and Cell, Journal Year: 2025, Volume and Issue: 93, P. 102736 - 102736

Published: Jan. 10, 2025

Language: Английский

Citations

0