Plasma exosomes may mediate the development of lupus nephritis in patients with systemic lupus erythematosus DOI
Jie Liu,

Yuanju Liu,

Yinde Xu

et al.

Lupus, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Background Lupus nephritis (LN) is the most serious complication of systemic lupus erythematosus (SLE), and plasma exosomes may serve as a bridge. MicroRNAs (miRNAs) are abundant in exosomes, so this study aimed to explore role exosome-derived miRNA development LN. Methods The publicly available data containing exosomal miRNAs SLE patients healthy controls were researched, differential expression functional enrichment analysis was conducted. Then, from extracted, accuracy preliminarily verified. PKH26 dye used label detect whether can enter HK2 cells. Evaluation impact on cell viability done by utilizing CCK-8 assay. Flow cytometry measure apoptosis. Results Plasma successfully extracted identified. Through pulbilic subsequent qPCR validation, we observed that miR-20b-5p overexpressed patients, whereas miR-181a-2-3p downregulated. Then revealed these primarily regulate processes such apoptosis, autophagy, inflammation. flow conducted after co-incubation peripheral blood mononuclear cells confirmed indeed And without affecting activity. In addition, promote apoptosis autophagy. Overexpression could inhibit upregulate bcl2, beclin1. At same time, trend towards increased rates miR-20b-5p, although difference did not reach statistical significance. enhance caspase3 becin1 while suppressing bcl2 LC3β. Conclusion Our research indicates presence depletion mediate promotion autophagy cells, thereby causing kidney damage

Language: Английский

The Interplay Between Chromatin Remodeling and DNA Double-strand Break Repair: Implications for Cancer Biology and Therapeutics DOI Creative Commons
Liu‐Jun He, Jaeyoung Moon,

Chenghui Cai

et al.

DNA repair, Journal Year: 2025, Volume and Issue: 146, P. 103811 - 103811

Published: Jan. 15, 2025

Proper chromatin remodeling is crucial for many cellular physiological processes, including the repair of DNA double-strand break (DSB). While mechanism DSB well understood, connection between and remains incompletely elucidated. In this review, we aim to highlight recent studies demonstrating close relationship repair. We summarize impact on chromatin, nucleosome arrangement, organization, dynamics, conversely, role architecture in regulating Additionally, also contribution complexes cancer biology through discuss their potential as therapeutic targets cancer.

Language: Английский

Citations

1
Nuclear and genome dynamics underlying DNA double-strand break repair DOI
Irene Chiolo, Matthias Altmeyer, Gaëlle Legube

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

1
Compartmentalization of the DNA damage response: Mechanisms and functions DOI Creative Commons
Emile Alghoul, Jihane Basbous, Angelos Constantinou

et al.

DNA repair, Journal Year: 2023, Volume and Issue: 128, P. 103524 - 103524

Published: June 10, 2023

Cells have evolved an arsenal of molecular mechanisms to respond continuous alterations in the primary structure DNA. At cellular level, DNA damage response proteins accumulate at sites and organize into nuclear foci. As recounted by Errol Friedberg, pioneering work on repair 1930 s was stimulated collaborations between physicists geneticists. In recent years, introduction ideas from physics self-organizing compartments has taken field cell biology storm. Percolation phase separation theories are increasingly used model self-assembly compartments, called biomolecular condensates, that selectively concentrate molecules without a surrounding membrane. this review, we discuss these concepts context response. We how studies foci as condensates can link with physiological functions, provide new insights regulatory mechanisms, open perspectives for targeting responses therapeutic purposes.

Language: Английский

Citations

18
Histone H4K12 lactylation promotes malignancy progression in triple-negative breast cancer through SLFN5 downregulation DOI Creative Commons
Jingyi Li, Ziyu Chen, Mingming Jin

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 124, P. 111468 - 111468

Published: Oct. 11, 2024

Lactylation, a newly identified post-translational modification, is uncertain in its implication triple-negative breast cancer (TNBC). In this study, we analyzed 60 TNBC samples using immunohistochemical staining and revealed elevated levels of pan-lactylated proteins specific histone H4K12 lactylation tumor tissues, correlating with progression. Lactate exposure cell lines significantly induced lysine at the site, leading to alterations gene profiles reduced apoptosis. These effects were attenuated by DCA or sodium Oxamate, inhibitors endogenous lactate production. Gene sequencing showed an increase Schlafen 5 (SLFN5) expression cells treated contrasting exposure. Analysis tissues negative correlation between SLFN5 protein levels. Overexpression countered on apoptosis growth, highlighting pivotal role malignancy. CUT&Tag indicated that lactylated potentially binds promoter region. Luciferase reporter assays further verified lactate-induced suppression activity mediated wild-type H4K12, but not R A mutants, both vitro vivo detection response Oxamate stimulation. results establish lactylation, cells, specifically suppresses expression, contributing Our findings illuminate critical lactylation-dependent carcinogenic pathway TNBC.

Language: Английский

Citations

5
Mouse Slfn8 and Slfn9 genes complement human cells lacking SLFN11 during the replication stress response DOI Creative Commons

Erin Alvi,

Ayako L. Mochizuki,

Y Katsuki

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Oct. 13, 2023

The Schlafen (SLFN)11 gene has been implicated in various biological processes such as suppression of HIV replication, replication stress response, and sensitization cancer cells to chemotherapy. Due the rapid diversification SLFN family members, it remains uncertain whether a direct ortholog human SLFN11 exists mice. Here we show that mSLFN8/9 hSLFN11 were rapidly recruited microlaser-irradiated DNA damage tracks. Furthermore, Slfn8/9 expression could complement loss

Language: Английский

Citations

8
Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone DOI Creative Commons
Emily S. Norton, Lauren Whaley, Vanessa K. Jones

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(32)

Published: Aug. 7, 2024

Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to lateral ventricles (LVs) more aggressive, potentially because of subventricular zone contact. Despite this, cross-talk between neural stem/progenitor cells (NSC/NPCs) not well understood. Using cell-specific proteomics, we show that LV-proximal prevents neuronal maturation NSCs through induction senescence. In addition, tumor-initiating (BTICs) increase expression cathepsin B (CTSB) upon interaction with NPCs. Lentiviral knockdown recombinant protein experiments reveal both cell-intrinsic soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble stalls NPCs while promoting senescence, providing a link LV-tumor proximity neurogenesis disruption. Last, up-regulation patients, showing relevance this human biology. These results demonstrate value proteomic analysis tumor microenvironment research provide direction for new therapeutic strategies GBM.

Language: Английский

Citations

2
Genome-wide profiling of DNA repair proteins in single cells DOI Creative Commons
Kim L. de Luca, Pim M. J. Rullens, Magdalena A. Karpińska

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 21, 2024

Accurate repair of DNA damage is critical for maintenance genomic integrity and cellular viability. Because occurs non-uniformly across the genome, single-cell resolution required proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis protein localization in single human cells using DamID ChIC sequencing techniques. This study reports genome-wide binding profiles response to double-strand breaks induced by AsiSI, explores variability locations associated features context spatial genome organization. By unbiasedly detecting factor localization, find that proteins often occupy entire topologically associating domains, mimicking chromatin loop anchoring. Moreover, demonstrate formation multi-way hubs damage. Notably, larger show increased coordination binding, suggesting preference cooperative mechanisms. Together, our work offers insights into heterogeneous processes underlying stability cells. crucial preventing disease. authors adapt omics technologies map location showing

Language: Английский

Citations

2
Genome-wide profiling of DNA repair identifies higher-order coordination in single cells DOI Creative Commons
Kim L. de Luca, Pim M. J. Rullens,

Magdalena Anna Karpińska

et al.

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

Published: May 11, 2023

Abstract Accurate repair of DNA damage is critical for maintenance genomic integrity and cellular viability. Because occurs non-uniformly across the genome, single-cell resolution required proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis protein localization in single cells using DamID ChIC sequencing techniques. This study reports genome-wide binding profiles response to double-strand breaks induced by AsiSI, explores variability locations associated features context spatial genome organization. By unbiasedly detecting factor localization, find that proteins often occupy entire topologically associating domains, mimicking chromatin loop anchoring. Moreover, demonstrate formation multi-way hubs damage. Notably, larger show increased coordination binding, suggesting preference cooperative mechanisms. Together, our work offers new insights into heterogeneous processes underlying stability cells.

Language: Английский

Citations

3
Repair of DNA double-strand breaks leaves heritable impairment to genome function DOI Creative Commons
Susanne C. S. Bantele, Irene Mordini, Alva Biran

et al.

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

Published: Aug. 29, 2023

Abstract Upon DNA breakage, a genomic locus undergoes alterations in 3-D chromatin architecture to facilitate signaling and repair. While cells possess mechanisms repair damaged DNA, it is unknown whether the surrounding restored its naïve state. We show that single double-strand break (DSB) within topologically-associated domain (TAD) harboring conformation-sensitive genes causes lasting alterations, which persist after completion of feature structural changes, compaction loss local RNA species. Unexpectedly, these newly-acquired features post-repair are transmitted daughter manifest as heritable impairments gene expression. These findings uncover hitherto concealed dimension we term fatigue, confers impairment function beyond

Language: Английский

Citations

3
The role of SLFN11 in DNA replication stress response and its implications for the Fanconi anemia pathway DOI
Anfeng Mu, Yusuke Okamoto, Y Katsuki

et al.

DNA repair, Journal Year: 2024, Volume and Issue: 141, P. 103733 - 103733

Published: July 24, 2024

Language: Английский

Citations

0