Similar Datasets
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
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 | GSE165468 | GEO
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
Project description:A major stress response influenced by microRNAs (miRNAs) 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. miR-340-5p 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, 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 removing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in pathologies of human aging.
| S-EPMC8287953 | biostudies-literature
Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis
| PRJNA694654 | ENA
Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (ATAC-Seq)
| PRJNA694653 | ENA
Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 1)
| PRJNA694655 | ENA
Project description:Suppression of LBR by miR-340 disrupts chromatin, promotes cell senescence, and enhances senolysis (RNA-Seq 2)
| PRJNA694657 | ENA
Project description:miR-30 is a microRNA frequently overexpressed in human cancers. However, the biological consequence of miR-30 overexpression in cancer has been unclear. In a genetic screen, miR-30 was found to abrogate oncogenic-induced senescence, a key tumor-suppressing mechanism that involves DNA damage responses, activation of p53 and induction of p16INK4A. In cells and mouse models, miR-30 disrupts senescence and promotes cancer by suppressing 2 targets, CHD7 and TNRC6A. We show that while CHD7 is a transcriptional coactivator essential for induction of p16INK4A in senescent cells, TNRC6A, a miRNA machinery component, is required for expression and functionality of DNA damage response RNAs (DDRNAs) that mediate DNA damage responses and p53 activation by orchestrating histone modifications, chromatin remodeling and recruitment of DNA damage factors at damaged sites. Thus, miR-30 inhibits both p16INK4A and p53, 2 key senescence effectors, leading to efficient senescence disruption. These findings have identified novel signaling pathways mediating oncogene-induced senescence and tumor-suppression, and revealed the molecular and cellular mechanisms underlying the oncogenic activity of miR-30. Thus, the miR-30/CHD7/TNRC6A pathway is potentially a novel diagnostic biomarker and therapeutic target for cancer.
| S-EPMC6195819 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) function as important regulators of gene expression involved in tumor pathogenesis, including retinoblastoma. However, the expression profiles and potential roles in retinoblastoma are still largely unclear.Material and methodsDifferentially expressed miRNAs (DEmiRs) and genes (DEGs) in retinoblastoma were extracted from Gene Expression Omnibus (GEO) repository. Expression levels of miR-340 and WIF1 were detected in retinoblastoma tissues and cell lines by qRT-PCR. Both gain-of-function and loss-of-function experiments were performed to explore the effects of miR-340 on cell proliferation, migration and invasion. Bioinformatics analysis and luciferase reporter assay were used to explore the interaction between miR-340 and WIF1.ResultsA total of 11 DEmiRs were identified in retinoblastoma tissue and blood samples. Among them, we validated that miR-340 was the most highly expressed miRNA and correlated with tumor size, ICRB stage and optic nerve invasion. miR-340 was observed to enhance the proliferation, migration and invasion capacity of retinoblastoma cells. We then identified 26 DEGs from 3 retinoblastoma GEO datasets and subsequently constructed a miRNA-mRNA regulatory network. Further analysis revealed that WIF1 was a direct target of miR-340. Moreover, overexpression of WIF1 could repress retinoblastoma progression induced by miR-340 in vitro and in vivo.ConclusionCollectively, miR-340 functioned as an oncomiRNA to promote retinoblastoma cell proliferation, migration and invasion via regulating WIF1. Our data also provided multiple miRNAs and genes that may contribute to a better understanding of retinoblastoma pathogenesis.
| S-EPMC8187089 | biostudies-literature