The emerging role of miRNA-132/212 cluster in neurologic and cardiovascular diseases: Neuroprotective role in cells with prolonged longevity

Fatimy, Rachid El; Boulaassafre, Soukayna; Bouchmaa, Najat; Khayari, Abdellatif El; Vergely, Catherine; Malka, G.; Rochette, Luc

doi:10.1016/j.mad.2021.111566

Cited by 9 publications

(4 citation statements)

References 175 publications

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“…ncRNAs, especially miRNAs and lncRNAs, have been shown to play an important role in the pathogenesis of many diseases. miRNA-132/212 promotes axonal evolution, neural migration, plasticity, and has very promising applications in neurodegenerative diseases such as Alzheimer's, Parkinson's, and epilepsy (11).…”

Section: Reviewmentioning

confidence: 99%

Current status and perspectives of non-coding RNA and phase separation interactions

Gao

Liu

et al. 2022

BST

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Section: Reviewmentioning

confidence: 99%

Current status and perspectives of non-coding RNA and phase separation interactions

Gao

Liu

et al. 2022

BST

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“…MicroRNAs (miRNAs, miRs) from plasma exosomes have been reported to be ideal biomarkers for the early identification of cardiovascular disease and to have great potential for therapeutic and other applications (11,12). There is evidence to suggest that a series of important physiological processes, including the survival, proliferation and angiogenesis of cardiomyocytes are regulated by miRNAs (13,14). In addition, miRNAs have been shown to stimulate cardiomyocyte proliferation and promote cardiac repair (15,16).…”

Section: Introductionmentioning

confidence: 99%

Exosomal miR‑152‑5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes

et al. 2023

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Acute myocardial infarction (AMI) is a fatal cardiovascular disease with a high mortality rate. The discovery of effective biomarkers is crucial for the diagnosis and treatment of AMI. In the present study, miRNA sequencing and reverse transcription-quantitative polymerase chain reaction techniques revealed that the expression of exosome derived miR-152-5p was significantly downregulated in patients with AMI compared with healthy controls. A series of functional validation experiments were then performed using H9c2 cardiomyocytes. Following transfection of the cardiomyocytes using an miR-152-5p inhibitor, immunofluorescence staining of a-smooth muscle actin revealed a marked increase in fibrosis. Western blotting revealed that the expression levels of the apoptotic protein Bax, TNF-α and collagen-associated proteins were significantly increased, whereas those of the apoptosis-inhibiting factor Bcl-2 and vascular endothelial growth factor A were significantly decreased. Furthermore, the binding of Rho GTPase-activating protein 6 (ARHGAP6) to miR-152-5p was predicted using an online database and verified using a dual-luciferase reporter gene assay. The transfection of cardiomyocytes with miR-152-5p mimics was found to inhibit the activation of ARHGAP6 and Rho-associated coiled-coil containing kinase 2 (ROCK2). These results suggest that miR-152-5p targets ARHGAP6 through the ROCK signaling pathway to inhibit AMI, which implies that miR-152-5p may be a diagnostic indicator and potential target for treatment of myocardial infarction.

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“…Similarly, synthetic antagomiRs silence the function of their cognate endogenous miRs. Although miR mimics and antagomiRs have been tested as therapeutic tools for obesity, T2DM, insulin resistance, and cardiovascular disease, they have met with limited success so far (32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

miR-10a-3p modulates adiposity and suppresses adipose inflammation through TGF-β1/Smad3 signaling pathway

et al. 2023

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BackgroundObesity is a multifactorial disease characterized by an enhanced amount of fat and energy storage in adipose tissue (AT). Obesity appears to promote and maintain low-grade chronic inflammation by activating a subset of inflammatory T cells, macrophages, and other immune cells that infiltrate the AT. Maintenance of AT inflammation during obesity involves regulation by microRNAs (miRs), which also regulate the expression of genes implicated in adipocyte differentiation. This study aims to use ex vivo and in vitro approaches to evaluate the role and mechanism of miR-10a-3p in adipose inflammation and adipogenesis.MethodsWild-type BL/6 mice were placed on normal (ND) and high-fat diet (HFD) for 12 weeks and their obesity phenotype, inflammatory genes, and miRs expression were examined in the AT. We also used differentiated 3T3-L1 adipocytes for mechanistic in vitro studies.ResultsMicroarray analysis allowed us to identify an altered set of miRs in the AT immune cells and Ingenuity pathway analysis (IPA) prediction demonstrated that miR-10a-3p expression was downregulated in AT immune cells in the HFD group as compared to ND. A molecular mimic of miR-10a-3p reduced expression of inflammatory M1 macrophages, cytokines, and chemokines, including transforming growth factor-beta 1 (TGF-β1), transcription factor Krüppel-like factor 4 (KLF4), and interleukin 17F (IL-17F) and induced expression of forkhead box P3 (FoxP3) in the immune cells isolated from AT of HFD-fed mice as compared to ND. In differentiated 3T3-L1 adipocytes, the miR-10a-3p mimics also reduced expression of proinflammatory genes and lipid accumulation, which plays a role in the dysregulation of AT function. In these cells, overexpression of miR-10a-3p reduced the expression of TGF-β1, Smad3, CHOP-10, and fatty acid synthase (FASN), relative to the control scramble miRs.ConclusionOur findings suggest that miR-10a-3p mimic mediates the TGF-β1/Smad3 signaling to improve metabolic markers and adipose inflammation. This study provides a new opportunity for the development of miR-10a-3p as a novel therapeutic for adipose inflammation, and its associated metabolic disorders.

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The emerging role of miRNA-132/212 cluster in neurologic and cardiovascular diseases: Neuroprotective role in cells with prolonged longevity

Cited by 9 publications

References 175 publications

Current status and perspectives of non-coding RNA and phase separation interactions

Current status and perspectives of non-coding RNA and phase separation interactions

Exosomal miR‑152‑5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes

miR-10a-3p modulates adiposity and suppresses adipose inflammation through TGF-β1/Smad3 signaling pathway

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