Senescence-associated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes

Banerjee, Joyita; Roy, S.; Dhas, Yogita

doi:10.1007/s10238-019-00593-4

Cited by 18 publications

(7 citation statements)

References 54 publications

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“…Very recently, Alessia et al demonstrated miR-126 has linked with Fabry disease (FD) and premature aging [ 16 ]. Another study showed that in the middle age type-2 diabetic patients, senescence was associated with reduced miR-126 levels [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

Sheikh

Almaeen

Alduraywish

et al. 2022

Oxidative Medicine and Cellular Longevity

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The aim of the study was to explore the clinical impact of circulatory miR-126 as a candidate for novel biomarker in patients with coronary artery disease (CAD) and its protective role against hypoxia/reoxygenation- (H/R-) exposed HUVEC cellular injury. A total of 278 subjects, which included 153 subjects with angiographically confirmed CAD, 70 unstable angina subjects, and 55 healthy individuals, along with 18-hour HR-induced HUVECs were recruited in this study. Plasma miR-126 levels were significantly downregulated in stable and unstable CAD patients as well as 18-hour HR-exposed HUVECs as compared with controls. Stable and unstable CAD subjects were significantly differentiated from healthy individuals with a predictive value of AUC 0.903 and 0.923, respectively. Moreover, peripheral circulatory miR-126 expressions in elderly (71-90 years) stable and unstable CAD patients were comparatively lower than younger (30-50 years) subjects. The caspase-3 activity, intracellular ROS concentrations, and cellular viabilities were evidently increased in 18-hour HR-exposed HUVECs than in normal cells ( P < 0.001 ). On the contrary, mimic expressions of miR-126 prominently reduced caspase-3 activity and intracellular ROS levels and markedly enhanced HUVEC cellular viabilities ( P < 0.001 ). LRP6 expressions were significantly elevated in HR-induced HUVECs, whereas overexpression of miR-126 remarkably decreased LRP6 expressions ( P < 0.001 ). Plasma miR-126 could be used as a novel biomarker for early prediction of CAD subjects. Overexpression of miR-126 significantly improved HUVEC cellular viabilities by downregulation of LRP6 protein expression, suggesting a potential therapeutic target for CAD patients.

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Section: Discussionmentioning

confidence: 99%

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

Sheikh

Almaeen

Alduraywish

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…miR‐34a is a multifunctional miRNA that plays an important role in many physiological and pathological processes including aging, atherosclerosis, and CHD. One study found that the expression level of miR‐34a in the heart tissues of elderly patients was significantly increased and related to the apoptosis, hypertrophy, fibrosis, and decreased compliance of cardiomyocytes (Banerjee et al, 2019). Furthermore, inhibiting the expression of miR‐34a in cardiomyocytes reduced apoptosis by upregulating phosphatase nuclear targeting subunit (PNUTS), which reduced the DNA damage response (Boon et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

miR‐34a attenuates myocardial fibrosis in diabetic cardiomyopathy mice via targeting Pin‐1

Zhang

Bai

2020

Cell Biology International

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Diabetic cardiomyopathy (DCM) is characterized by myocardial hypertrophy and fibrosis. This study aimed to investigate the effects of microRNA (miR)‐34a on myocardial fibrosis in DCM and its potential mechanism of targeting Pin‐1 signaling. Vimentin and Pin‐1 proteins in mouse cardiac tissues were detected by immunohistochemical staining. Locked nucleic acid in situ hybridization was used to measure miR‐34a expression in cardiac tissues. Primary mouse cardiac fibroblasts (CFs) were transfected with a mimics control/miR‐34a mimics or Pin‐1 plasmid and cultured in high‐glucose (HG) Dulbecco's modified Eagle's medium. The miR‐34a levels were measured by quantitative polymerase chain reaction. The apoptosis and viability of transfected cells were detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling and Cell Counting Kit‐8 assays respectively. A cell migration experiment and dual‐luciferase reporter assay were also performed. The body weight and fasting blood glucose of DCM mice were significantly higher than those in the control (CTL) group. In addition, DCM mice had decreased serum insulin levels and impaired cardiac function. The number of CFs in the DCM group was higher than in the CTL group and Pin‐1 expression was upregulated. The expression level of miR‐34a in the cardiac tissue of mice in the DCM group was obviously downregulated compared with the CTL group. The HG stimulation of CFs for 48 h significantly downregulated the expression level of miR‐34a and was associated with increased Type I collagen expression, cell viability, and migration and decreased apoptosis. However, these effects could be reversed by overexpressing miR‐34a in HG‐induced CFs. Furthermore, we found that Pin‐1 was a direct target of miR‐34a. Our results suggest that miR‐34a can attenuate myocardial fibrosis in DCM by reducing Type I collagen production, cell viability, and migration and increasing the apoptosis of CFs by targeting Pin‐1 signaling.

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“…They found an upregulation of miR-34a in T2DM and T1DM subjects [ 187 ]. Similarly, in 2020 Banerjee et al described increased levels of circulating miR-34a and oxidative stress markers in the plasma of T2DM middle-aged Indians ([ 188 ]; Table 2 ).…”

Section: Mir-34a In Vd And-associated Complicationsmentioning

confidence: 97%

MicroRNA-34a: the bad guy in age-related vascular diseases

Raucci

Macrì

Castiglione

et al. 2021

Cell. Mol. Life Sci.

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The age-related vasculature alteration is the prominent risk factor for vascular diseases (VD), namely, atherosclerosis, abdominal aortic aneurysm, vascular calcification (VC) and pulmonary arterial hypertension (PAH). The chronic sterile low-grade inflammation state, alias inflammaging, characterizes elderly people and participates in VD development. MicroRNA34-a (miR-34a) is emerging as an important mediator of inflammaging and VD. miR-34a increases with aging in vessels and induces senescence and the acquisition of the senescence-associated secretory phenotype (SASP) in vascular smooth muscle (VSMCs) and endothelial (ECs) cells. Similarly, other VD risk factors, including dyslipidemia, hyperglycemia and hypertension, modify miR-34a expression to promote vascular senescence and inflammation. miR-34a upregulation causes endothelial dysfunction by affecting ECs nitric oxide bioavailability, adhesion molecules expression and inflammatory cells recruitment. miR-34a-induced senescence facilitates VSMCs osteoblastic switch and VC development in hyperphosphatemia conditions. Conversely, atherogenic and hypoxic stimuli downregulate miR-34a levels and promote VSMCs proliferation and migration during atherosclerosis and PAH. MiR34a genetic ablation or miR-34a inhibition by anti-miR-34a molecules in different experimental models of VD reduce vascular inflammation, senescence and apoptosis through sirtuin 1 Notch1, and B-cell lymphoma 2 modulation. Notably, pleiotropic drugs, like statins, liraglutide and metformin, affect miR-34a expression. Finally, human studies report that miR-34a levels associate to atherosclerosis and diabetes and correlate with inflammatory factors during aging. Herein, we comprehensively review the current knowledge about miR-34a-dependent molecular and cellular mechanisms activated by VD risk factors and highlight the diagnostic and therapeutic potential of modulating its expression in order to reduce inflammaging and VD burn and extend healthy lifespan.

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Senescence-associated miR-34a and miR-126 in middle-aged Indians with type 2 diabetes

Cited by 18 publications

References 54 publications

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

miR‐34a attenuates myocardial fibrosis in diabetic cardiomyopathy mice via targeting Pin‐1

MicroRNA-34a: the bad guy in age-related vascular diseases

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