MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling

Olivieri, Fabiola; Lazzarini, Raffaella; Recchioni, Rina; Marcheselli, Fiorella; Rippo, Maria Rita; Nuzzo, Silvia; Albertini, Maria Cristina; Graciotti, Laura; Babini, Lucia; Mariotti, S.; Spada, Giorgio; Abbatecola, Angela Marie; Antonicelli, Roberto; Franceschi, Claudio; Procopio, Antonio Domenico

doi:10.1007/s11357-012-9440-8

Cited by 184 publications

(174 citation statements)

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“…miR‐9 may also have a role during aging. While miR‐9 can target prelamin A, thereby preventing the expression of progerin in models of Hutchinson‐Gilford progeria syndrome (HPGS) (Jung et al ., 2012), other studies (Olivieri et al ., 2013) and this report have observed that the expression of miR‐9 can increase during senescence. The ability of miR‐9 to downregulate CBX7 expression causing p16 INK4a induction and senescence could therefore provide an explanation for the role of miR‐9 in cancer and aging.…”

Section: Discussionmentioning

confidence: 52%

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

et al. 2015

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SummaryPolycomb repressive complexes (PRC1 and PRC2) are epigenetic regulators that act in coordination to influence multiple cellular processes including pluripotency, differentiation, cancer and senescence. The role of PRCs in senescence can be mostly explained by their ability to repress the INK4/ARF locus. CBX7 is one of five mammalian orthologues of Drosophila Polycomb that forms part of PRC1. Despite the relevance of CBX7 for regulating senescence and pluripotency, we have a limited understanding of how the expression of CBX7 is regulated. Here we report that the miR‐9 family of microRNAs (miRNAS) downregulates the expression of CBX7. In turn, CBX7 represses miR‐9‐1 and miR‐9‐2 as part of a regulatory negative feedback loop. The miR‐9/CBX7 feedback loop is a regulatory module contributing to induction of the cyclin‐dependent kinase inhibitor (CDKI) p16INK 4a during senescence. The ability of the miR‐9 family to regulate senescence could have implications for understanding the role of miR‐9 in cancer and aging.

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Section: Discussionmentioning

confidence: 52%

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

et al. 2015

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“…It is estimated that approximately one‐third of all animal genes are controlled by microRNAs, and thus, microRNAs exhibit a wide range of biological processes including aging (Breving & Esquela‐Kerscher, 2010). Indeed, several earlier studies were directed to examine the relationship between microRNAs and endothelial cell senescence (Menghini et al ., 2009; Zhao et al ., 2010; Jong et al ., 2013; Olivieri et al ., 2013; Zhu et al ., 2013). Our present comprehensive microarray analysis revealed that the microRNA with the third highest augmented expression in senescent HUVECs was miR‐22‐3p and that it had a binding site on the 3′ UTR of VASH1 mRNA.…”

Section: Discussionmentioning

confidence: 99%

Age‐associated downregulation of vasohibin‐1 in vascular endothelial cells

2016

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SummaryVasohibin‐1 (VASH1) is an angiogenesis‐inhibiting factor synthesized by endothelial cells (ECs) and it also functions to increase stress tolerance of ECs, which function is critical for the maintenance of vascular integrity. Here, we examined whether the expression of VASH1 would be affected by aging. We passaged human umbilical vein endothelial cells (HUVECs) and observed that VASH1 was downregulated in old HUVECs. This decrease in VASH1 expression with aging was confirmed in mice. To explore the mechanism of this downregulation, we compared the expression of microRNAs between old and young HUVECs by performing microarray analysis. Among the top 20 microRNAs that were expressed at a higher level in old HUVECs, the third highest microRNA, namely miR‐22‐3p, had its binding site on the 3′ UTR of VASH1 mRNA. Experiments with microRNA mimic and anti‐miR revealed that miR‐22‐3p was involved at least in part in the downregulation of VASH1 in ECs during replicative senescence. We then clarified the significance of this defective expression of VASH1 in the vasculature. When a cuff was placed around the femoral arteries of wild‐type mice and VASH1‐null mice, neointimal formation was augmented in the VASH1‐null mice accompanied by an increase in adventitial angiogenesis, macrophage accumulation in the adventitia, and medial/neointimal proliferating cells. These results indicate that in replicative senescence, the downregulation of VASH1 expression in ECs was caused, at least in part, by the alteration of microRNA expression. Such downregulation of VASH1 might be involved in the acceleration of age‐associated vascular diseases.

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“…Отдельные микроРНК играют важную роль в старении эндотелия. Так, например, miRNA-146a задерживает старение эндотелиальных клеток [19], а miRNA-217 и miRNA-34а ускоряют старение эндотелиоцитов [20].…”

Section: роль микрорнк в дисфункции эндотелияunclassified

Epigenetic factors in atherogenesis: microRNA

et al. 2016

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MicroRNAs (miRNAs) are small (~22 nucleotides in length) noncoding RNA sequences regulating gene expression at posttranscriptional level. MicroRNAs bind complementarily to certain mRNA and cause gene silencing. The involvement of miRNAs in the regulation of lipid metabolism, inflammatory response, cell cycle progression and proliferation, oxidative stress, platelet activation, endothelial and vascular smooth muscle cells (VSMC) function, angiogenesis and plaque formation and rapture indicates important roles in the initiation and progression of atherosclerosis. The key role of microRNAs in pathophysiology of cardiovascular diseases (CVDs), including atherosclerosis, was demonstrated in recent studies. Creating antisense oligonucleotides is a novel technique for selective changes in gene expression both in vitro and in vivo. In this review, we draw attention to the role of miRNAs in atherosclerosis progression, using miRNA as the potential biomarkers and targets in the CVDs, as well as possible application of antisense oligonucleotides

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MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling

Cited by 184 publications

References 50 publications

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

Age‐associated downregulation of vasohibin‐1 in vascular endothelial cells

Epigenetic factors in atherogenesis: microRNA

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MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling

Cited by 184 publications

References 50 publications

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16INK4a

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16INK4a

Age‐associated downregulation of vasohibin‐1 in vascular endothelial cells

Epigenetic factors in atherogenesis: microRNA

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CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a