Activation of glucocorticoid receptor signaling inhibits KSHV-induced inflammation and tumorigenesis DOI Creative Commons
Luping Chen, Ling Ding, Xian Wang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 14, 2023

Hyperinflammation is the hallmark of Kaposi's sarcoma (KS), most common cancer in AIDS patients caused by sarcoma-associated herpesvirus (KSHV) infection. However, role and mechanism induction inflammation KS remain unclear. In a screening for inhibitors KSHV-induced oncogenesis, over half identified candidates were anti-inflammatory agents including dexamethasone functions activating glucocorticoid receptor (GR) signaling. Here, we examined mediating inflammation. We found that numerous inflammatory pathways activated KSHV-transformed cells. Particularly, interleukin-1 alpha (IL-1α) IL-1 antagonist (IL-1Ra) from family induced suppressed cytokines, respectively. KSHV miRNAs mediated IL-1α while both vFLIP IL-1Ra suppression. Furthermore, GR signaling was inhibited cells, which vCyclin. Dexamethasone treatment signaling, cell proliferation colony formation soft agar cells but had minimal effect on matched primary Consequently, initiation growth tumors mice. Mechanistically, expression. Treatment with recombinant protein rescued inhibitory overexpression weak inhibition IκBα expression resulting NF-κB pathway These results reveal an important can be dexamethasone-activated identify IL-1-mediated as potential therapeutic target malignancies.

Language: Английский

Blood-Based Whole-Genome Methylation Analysis of Yili Horses Pre- and Post-Racing DOI Creative Commons
Jianwen Wang, Wanlu Ren,

Zexu Li

et al.

Animals, Journal Year: 2025, Volume and Issue: 15(3), P. 326 - 326

Published: Jan. 24, 2025

This study aims to analyze the whole-genome DNA methylation differences in Yili horses before and after racing, with goal of identifying differentially methylated genes associated racing performance exploring epigenetic mechanisms underlying exercise horses. Blood samples were collected from jugular veins top 3 a 5000 m race, which included 25 competitors, both prior within 5 min race. Genomic was extracted, followed by sequencing using Whole-Genome Bisulfite Sequencing (WGBS) assess levels, regions (DMRs), (DMGs). Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses performed on identified DMGs select candidate potentially equine exercise. A total 18,374 CG regions, 254 CHG 584 CHH identified. 4293 anchored gene bodies 2187 promoter regions. Functional analysis revealed that these mainly enriched terms related binding kinase activity, as well pathways such PI3K-Akt signaling Kaposi sarcoma-associated herpesvirus infection. Further indicated IFNAR2, FGF4, DGKH could be potential athletic performance. The findings this contribute understanding regulatory performance, providing reference for further in-depth research horse racing.

Language: Английский

Citations

1
Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells DOI Creative Commons

Francesca Panico,

Davida Mirra, Giuseppe Petito

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1014 - 1014

Published: April 22, 2025

Background: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as target. However, the underlying mechanisms of T2 related to diseases are poorly understood. Aims: To investigate protective action on an vitro model human epithelial alveolar cells. Methods: ATP synthesis cytochrome c oxidase (COX) activity, marker function, was assessed A549 cells pretreated with exposed CS using bioluminescence assay Oroboros 2k-Oxygraph system, respectively. An evaluation oxidative status conducted by assessing superoxide radical production, dismutase (SOD) H2O2 levels. Moreover, we investigated mass via Mito-Tracker Green (MTG) staining flow cytometry analysis. Results: significantly reduced production. pretreatment found prevent impairments synthesis, enhancing COX activity. Additionally, 2 h CS-exposed mitigated stress, thereby SOD activity reducing anion Finally, MTG labeling correlated gain, which associated cell senescence. Unexpectedly, not able this increment, probably due its rapid mode action. Conclusions: Our results provide new insights into effects against damage.

Language: Английский

Citations

0
Viral oncogenesis in cancer: from mechanisms to therapeutics DOI Creative Commons
Qing Xiao, Yi Liu, Tingting Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: May 11, 2025

Abstract The year 2024 marks the 60th anniversary of discovery Epstein-Barr virus (EBV), first confirmed to cause human cancer. Viral infections significantly contribute global cancer burden, with seven known Group 1 oncogenic viruses, including hepatitis B (HBV), papillomavirus (HPV), EBV, Kaposi sarcoma-associated herpesvirus (KSHV), C (HCV), T-cell leukemia type (HTLV-1), and immunodeficiency (HIV). These viruses induce cellular transformation development by altering various biological processes within host cells, particularly under immunosuppression or co-carcinogenic exposures. are primarily associated hepatocellular carcinoma, gastric cancer, cervical nasopharyngeal sarcoma, lymphoma, adult leukemia/lymphoma. Understanding mechanisms viral oncogenesis is crucial for identifying characterizing early virus-related cancers, providing new targets strategies treatment prevention. This review outlines epidemiology tumors, milestone events in research, process which infect target cells. It then focuses on molecular these tumors directly indirectly, regulation oncogenes tumor suppressor genes, induction genomic instability, disruption regular life cycle immune suppression, chronic inflammation, inducing angiogenesis. Finally, current therapeutic recent advances preclinical clinical research discussed.

Language: Английский

Citations

0
METTL16 controls Kaposi’s sarcoma-associated herpesvirus replication by regulating S-adenosylmethionine cycle DOI Creative Commons
Xinquan Zhang, Wen Meng, Jian Feng

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 6, 2023

Abstract Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) consists of latent and lytic replication phases, both which are important for the development KSHV-related cancers. As one most abundant RNA modifications, N 6 -methyladenosine (m A) its related complexes regulate KSHV life cycle. However, role METTL16, a newly discovered methyltransferase, in cycle remains unknown. In this study, we have identified suppressive METTL16 replication. knockdown increased while overexpression reduced binding to writing m A on MAT2A transcript essential splicing, maturation expression. rate-limiting enzyme methionine- S -adenosylmethionine (SAM) cycle, catalyzes conversion L-methionine SAM required transmethylation protein, DNA RNA, transamination polyamines, transsulfuration cystathionine. Consequently, or chemical inhibition intracellular level enhanced contrast, treatment was sufficient inhibit reverse effect program caused by knockdown. Mechanistically, decreased reactive oxygen species altering glutathione level, is efficient These findings demonstrate that suppresses modulating maintain redox homeostasis, thus illustrating linkage with specific cellular metabolic oxidative conditions.

Language: Английский

Citations

9
RUNX3 inhibits KSHV lytic replication by binding to the viral genome and repressing transcription DOI
Pengyu Ren, Danping Niu, Sijia Chang

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(2)

Published: Jan. 10, 2024

Kaposi's sarcoma-associated herpesvirus (KSHV) belongs to the gamma family, which can cause human malignancies including Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman's diseases. KSHV typically maintains a persistent latent infection within host. However, after exposure intracellular or extracellular stimuli, lytic replication be reactivated. The reactivation process of triggers innate immune response limit viral replication. Here, we found that transcriptional regulator RUNX3 is transcriptionally upregulated by NF-κB signaling pathway in KSHV-infected SLK cells B during reactivation. Notably, knockdown significantly promotes as well gene transcription KSHV. Consistent with this finding, overexpression impairs Mechanistically, binds genome limits through repression, related its DNA- ATP-binding ability. has also evolved corresponding strategies antagonize inhibition using protein RTA target for ubiquitination proteasomal degradation. Altogether, our study suggests RUNX3, novel host-restriction factor represses genes, may serve potential restrict transmission disease development.IMPORTANCEThe from important tumorigenicity. complex event, regulatory mechanisms are not fully elucidated. Our revealed host reactivation, repress genes. At late stage replication, utilizes mechanism involving degrade thus evading inhibition. This finding helps elucidate life cycle provide new clues development therapeutic KSHV-associated

Language: Английский

Citations

3
Targeting FoxO proteins induces lytic reactivation of KSHV for treating herpesviral primary effusion lymphoma DOI Creative Commons

Jun‐gang Lan,

Yeqing Wang,

Shusheng Yue

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(8), P. e1011581 - e1011581

Published: Aug. 18, 2023

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus consisting of both latent and lytic life cycles. Primary effusion lymphoma (PEL) aggressive B-cell lineage lymphoma, dominantly latently infected by KSHV. The infection KSHV persistent poses obstacle to killing tumor cells. Like the "shock kill" strategy designed eliminate HIV reservoir, methods that induce viral reactivation in viruses represent a unique antineoplastic strategy, as it could potentially increase specificity cytotoxicity cancer. Inspired this conception, we proposed induction from latency be potential therapeutic stratagem for KSHV-associated cancers. Oxidative stress, clinical hallmark PEL, one most prominent inducers reactivation. Paradoxically, found hydrogen peroxide (H2O2) triggers robust cytotoxic effects on KSHV-negative rather than KSHV-positive B cells dose-dependent manner. Mechanistically, identified forkhead box protein O1 (FoxO1) FoxO3 irrevocable antioxidant defense genes them are upregulated infection, which essential promoted ROS scavenging Pharmacological inhibition or functional knockdown either FoxO1 sufficient ablate ability therefore increases intracellular level further reverses active replication PEL cells, resulting tremendous cell death vitro vivo. Additionally, elevated inhibiting FoxO proteins sensitizes ROS-induced apoptosis. Our study demonstrated promising approach extended other virus-associated diseases.

Language: Английский

Citations

6
Association between human herpesvirus 8 and lipid profile in northwest China: A cross‐sectional study DOI
Jing-Zhan Zhang, Peng Wang, Tingting Li

et al.

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(8)

Published: Aug. 1, 2024

Abstract Human herpesvirus 8 (HHV‐8) infection shows obvious regional and ethnic differences. Although studies have shown that these differences may be associated with lipid metabolism, to date, no large‐scale explored this. This study the seropositivity rate of HHV‐8 among 2516 residents from 10 regions northwest China then correlates profile. The serological positivity was 15.6% all residents. seroprevalence ranged 11.2–27.6% different ethnicities. Across BMI levels, positive rates were 27.6%, 16.9%, 13.6% for a < 18.5, 18.5–24.9, ≥25, respectively. lower hypertensive people (12.6%) than non‐hypertensive (16.7%). Univariate logistic regression analyses revealed age, hypertension, systolic blood pressure, BMI, total cholesterol, high‐density lipoprotein cholesterol (HDL‐C) significantly correlated ( p 0.05). Multivariate analysis after adjusting confounding factors showed HDL‐C (odds ratio [OR]: 0.132, 95% confidence interval [CI], 0.082–0.212; 0.001) (OR: 0.959, CI 0.933–0.986; = 0.003) seropositivity. Subgroup concerning ethnicity, sex, or age demonstrated consistent relationship HDL‐C. results inconsistent in subgroups. However, Spearman's correlation between serum antibody titer levels linear seropositive individuals (ρ −0.080, 0.058). titers also not −0.015, 0.381). Low an independent risk factor infection, but there is significant titers.

Language: Английский

Citations

1
Pioneer factors in viral infection DOI Creative Commons

Eva Neugebauer,

Aura M. Bastidas-Quintero,

Daniel Weidl

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 9, 2023

Pioneer factors are transcription sharing the fascinating ability to bind compact chromatin and thereby alter its transcriptional fate. Most pioneer known for their importance during embryonic development, instance, in inducing zygotic genome activation or cell fate decision. Some actively induced downregulated by viral infection. With this, viruses capable modulate different signaling pathways resulting example MHC-receptor up/downregulation which contributes immune evasion. In this article, we review current state of research on how (Herpesviruses, Papillomaviruses Hepatitis B virus) use replication persistence host, as well development cancer.

Language: Английский

Citations

3
Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication DOI
Xia Cao, Q. Li, Xiaoli Li

et al.

AAPS PharmSciTech, Journal Year: 2023, Volume and Issue: 24(8)

Published: Nov. 28, 2023

Language: Английский

Citations

3
Activation of glucocorticoid receptor signaling inhibits KSHV-induced inflammation and tumorigenesis DOI Creative Commons
Luping Chen, Ling Ding, Xian Wang

et al.

mBio, Journal Year: 2023, Volume and Issue: 15(1)

Published: Dec. 20, 2023

ABSTRACT Hyperinflammation is the hallmark of Kaposi’s sarcoma (KS), most common cancer in AIDS patients caused by sarcoma-associated herpesvirus (KSHV) infection. However, role and mechanism induction inflammation KS remain unclear. In a screening for inhibitors KSHV-induced oncogenesis, over half identified candidates were anti-inflammatory agents including dexamethasone, which functions activating glucocorticoid receptor (GR) signaling. Here, we examined mediating inflammation. We found that numerous inflammatory pathways activated KSHV-transformed cells. Particularly, interleukin-1 alpha (IL-1α) IL-1 antagonist (IL-1Ra) from family induced suppressed cytokines, respectively. KSHV miRNAs mediated IL-1α while both vFLIP IL-1Ra suppression. Furthermore, GR signaling was inhibited cells, vCyclin. Dexamethasone treatment cell proliferation colony formation soft agar cells but had minimal effect on matched primary Consequently, dexamethasone initiation growth tumors mice. Mechanistically, expression. Treatment with recombinant protein rescued inhibitory overexpression weak inhibition IκBα expression resulting NF-κB pathway These results reveal an important can be dexamethasone-activated signaling, identify IL-1-mediated as potential therapeutic target malignancies. IMPORTANCE (KS) HIV-infected KS. this study, have shown mediates hyperinflammation inducing suppressing IL-1Ra. induce pathway. A agent blocks tumorigenesis to suppress This work has

Language: Английский

Citations

2