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Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis

ABSTRACT: Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis

PROVIDER: PRJNA694654 | ENA |

REPOSITORIES: ENA

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Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (ATAC-Seq)

Project description:The goal of this study was to identify accessible chromatin peaks in lamina-associated domains of senescent cells. To establish senescence we used ionizing radiation (IR), overexpression of miR-340-5p, and knockdown of Lamin B Receptor (LBR).One of the cellular processes influenced by microRNAs is senescence, a state of indefinite growth arrest triggered by sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as a novel miRNA that foments cellular senescence. miR340-5p was highly abundant in diverse senescence models, and miR-340-5p overexpression in proliferating cells rendered them senescent. Among the target mRNAs, miR-340-5p prominently reduced the levels of LBR mRNA, encoding Lamin B Receptor (LBR). Loss of LBR by ectopic overexpression of miR-340-5p derepressed heterochromatin in lamina-associated domains (LADs), promoting the expression of DNA repetitive elements characteristic of senescence. Importantly, overexpressing miR-340-5p enhanced cellular sensitivity to senolytic compounds, while antagonization of miR-340-5p reduced senescent-cell markers and engendered resistance to senolytic-induced cell death. We propose that miR-340-5p can be exploited for clearing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in aging human pathologies.

2021-06-25 | GSE165465 | GEO

Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 1)

Project description:One of the cellular processes influenced by microRNAs is senescence, a state of indefinite growth arrest triggered by sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as a novel miRNA that foments cellular senescence. miR340-5p was highly abundant in diverse senescence models, and miR-340-5p overexpression in proliferating cells rendered them senescent. Among the target mRNAs, miR-340-5p prominently reduced the levels of LBR mRNA, encoding Lamin B Receptor (LBR). Loss of LBR by ectopic overexpression of miR-340-5p derepressed heterochromatin in lamina-associated domains (LADs), promoting the expression of DNA repetitive elements characteristic of senescence. Importantly, overexpressing miR-340-5p enhanced cellular sensitivity to senolytic compounds, while antagonization of miR-340-5p reduced senescent-cell markers and engendered resistance to senolytic-induced cell death. We propose that miR-340-5p can be exploited for clearing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in aging human pathologies.

2021-06-25 | GSE165466 | GEO

Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 2)

2021-06-25 | GSE165468 | GEO

Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (ATAC-Seq)

Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (ATAC-Seq)

| PRJNA694653 | ENA

Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 1)

Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 1)

| PRJNA694655 | ENA

Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 2)

Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 2)

| PRJNA694657 | ENA

Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-25 | GSE165469 | GEO

Reduction of lamin B receptor levels by miR-340-5p disrupts chromatin, promotes cell senescence and enhances senolysis.

Project description: Not available

| S-EPMC8287953 | biostudies-literature

Transcriptome of LBR-null mouse kidneys

Project description:We tested overall gene expression change upon chromatin architecture disruption. RNA-seq was performed using nuclear architecture-disrupted mice carrying a loss-of-function mutation in LBR (Lbric-J/ic-J; LBR-null mice). LBR is an INM protein that tethers heterochromatin to the nuclear envelope whose level is decreased in various aging contexts.

2021-06-01 | GSE169240 | GEO

Photoactivatable senolysis with single-cell resolution reverses aging

Project description:Emerging evidence supports the use of pharmaceutical interventions to target senescent cells (SnCs) and induce their death (senolysis) to extend a healthy lifespan. The challenge then becomes how to achieve precise, broad-spectrum and tractable senolysis. To this end, we have designed a novel senotherapeutic agent with an unprecedented integrated strategy

2022-09-24 | GSE213846 | GEO

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