Reduction of lamin B receptor levels by miR-340-5p disrupts chromatin, promotes cell senescence and enhances senolysis
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Reduction of lamin B receptor levels by miR-340-5p disrupts chromatin, promotes cell senescence and enhances senolysis. / Herman, Allison B.; Anerillas, Carlos; Harris, Sophia C.; Munk, Rachel; Martindale, Jennifer L.; Yang, Xiaoling; Mazan-Mamczarz, Krystyna; Zhang, Yongqing; Heckenbach, Indra J.; Scheibye-Knudsen, Morten; De, Supriyo; Sen, Payel; Abdelmohsen, Kotb; Gorospe, Myriam.
I: Nucleic Acids Research, Bind 49, Nr. 13, 2021, s. 7389-7405.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Reduction of lamin B receptor levels by miR-340-5p disrupts chromatin, promotes cell senescence and enhances senolysis
AU - Herman, Allison B.
AU - Anerillas, Carlos
AU - Harris, Sophia C.
AU - Munk, Rachel
AU - Martindale, Jennifer L.
AU - Yang, Xiaoling
AU - Mazan-Mamczarz, Krystyna
AU - Zhang, Yongqing
AU - Heckenbach, Indra J.
AU - Scheibye-Knudsen, Morten
AU - De, Supriyo
AU - Sen, Payel
AU - Abdelmohsen, Kotb
AU - Gorospe, Myriam
N1 - Publisher Copyright: © 2021 Published by Oxford University Press on behalf of Nucleic Acids Research 2021.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1093/nar/gkab538
DO - 10.1093/nar/gkab538
M3 - Journal article
C2 - 34181735
AN - SCOPUS:85112127285
VL - 49
SP - 7389
EP - 7405
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 13
ER -
ID: 276271477