MicroRNAs as pharmacological targets in diabetes

Mao, Yiping; Mohan, Ramkumar; Zhang, Shungang; Tang, Xiaoqing

doi:10.1016/j.phrs.2013.06.005

Cited by 72 publications

(45 citation statements)

References 151 publications

(217 reference statements)

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“…As a key player in gene expression regulation, microRNAs (miRNAs) are endogenous, noncoding RNAs of 21-24 nucleotides that bind to the 3Ј-UTR of target mRNAs thereby repressing their translation and/or promoting their decay (23,24). With no exceptions to most eukaryotic cells, recent studies suggested that miRNAs have also emerged as important regulators in ␤-cell function and proliferation (25,26). Several miRNAs have been identified to function in controlling and maintaining ␤-cell proliferation and mass expansion through targeting various cellular signaling pathways.…”

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confidence: 99%

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells

Mohan

Mao

Zhang

et al. 2015

Journal of Biological Chemistry

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Background: MicroRNAs are noncoding RNAs and have emerged as important regulators in ␤-cell function. Results: miR-483 is highly expressed in ␤-cells but expressed at much lower levels in ␣-cells, and increased miR-483 induces insulin production in ␤-cells while repressing glucagon production in ␣-cells. Conclusion: miR-483 has opposite effects in ␣-and ␤-cells by targeting SOCS3. Significance: miR-483 is a potential therapeutic target for diabetes.

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confidence: 99%

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells

Mohan

Mao

Zhang

et al. 2015

Journal of Biological Chemistry

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“…That might explain, at least partially, the irreversibility of cardiovascular complications of long-standing uncontrolled diabetes often encountered in clinical care. Finally, MicroRNAs are also implicated in the pathophysiology of diabetes and its complications and could even be potential pharmacological targets [Mao et al 2013].…”

Section: Epigenetics In Vascular Diseasesmentioning

confidence: 99%

The emerging role of epigenetics in cardiovascular disease

Khalil

2014

Therapeutic Advances in Chronic Disease

109

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There is a worldwide epidemic of cardiovascular diseases causing not only a public health issue but also accounting for trillions of dollars of healthcare expenditure. Studies pertaining to epidemiology, pathophysiology, molecular biology, gene identification and genetic linkage maps have been able to lay a strong foundation for both the diagnosis and treatment of cardiovascular medicine. Although the concept of 'epigenetics' is not recent, the term in current usage is extended from the initial concept of 'controlling developmental gene expression and signaling pathways in undifferentiated zygotes' to include heritable changes to gene expression that are not from differences in the genetic code. The impact of epigenetics in cardiovascular disease is now emerging as an important regulatory key player at different levels from pathophysiology to therapeutics. This review focuses on the emerging role of epigenetics in major cardiovascular medicine specialties such as coronary artery disease, heart failure, cardiac hypertrophy and diabetes.

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“…Nonetheless, restoration of miRNA expression to normal levels appears as a potentially attractive therapeutic strategy. Several trials aiming at modulating the expression of specific miRNAs and restore their physiological levels are already on the way for other pathological conditions [77,78]. Depending on the expression levels of the candidate miRNA in diseased tissues and of the function of the non-coding RNA, two main strategies can be envisaged:…”

Section: Reparative Mirna Therapiesmentioning

confidence: 99%

Therapeutic potential of miRNAs in diabetes mellitus

Henaoui

Stoll

Tugay

et al. 2014

Expert Review of Endocrinology & Metabolism

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SummaryMicroRNAs are major regulators of gene expression that are emerging as central players in the development of many human diseases, including diabetes mellitus. In fact, diabetes manifestation is associated with alterations in the microRNA profile in insulin-secreting cells, insulin target tissues and, in case of long-term diabetes complications, in many additional organs. Diabetes results also in changes in the profile of microRNAs detectable in blood and other body fluids. This has boosted an ever increasing interest in the use of circulating microRNAs as potential biomarkers to predict the development of diabetes and its devastating complications. Moreover, promising approaches to correct the level of selected microRNAs are emerging, permitting to envisage new therapeutic strategies to treat diabetes and its complications.Key words: Diabetes mellitus; Insulin; pancreatic islet; microRNA; Gene expression; biomarker; diabetic complication; Adeno-associated virus 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 of target mRNAs that are initially recognized through base pairing to a conserved "seed" sequence corresponding to nucleotides 2-8 of the miRNAs, leading to inhibition of mRNA translational and/or to a decrease in messenger stability [2, 3]. A single miRNA typically controls hundreds of targets and each mRNA can be targeted by different miRNAs, conferring to this class of non-coding RNA molecules a huge regulatory potential [4]. In the past decade, a large body of evidence has been accumulated pointing to a role for miRNAs in the etiology and pathogenesis of diabetes and its complications. Indeed, alterations in the level of these non-coding RNAs has been observed both in insulin-secreting cells and in insulin-target tissues isolated from diabetes animal models or diabetic patients [5]. Moreover, changes in miRNA expression have been associated with long-term diabetes complications including neuropathy, retinopathy, renal failure and macrovascular diseases. Page 1 of 36 Expert Review of Endocrinology & MetabolismThe first demonstration of the involvement of miRNAs in the control of specialized β-cell functions has been provided ten years ago by Poy et al. who showed that inappropriate levels of miR-375, one of the most abundant miRNAs present in β-cells, can affect insulin secretion [6]. Later on, this and several other miRNAs including miR-15a/b, miR-16, miR-195, miR-503, miR-451, miR-214, miR-9, miR-124a, miR-7 and miR-376 were demonstrated to play important roles in the differentiation of pancreatic islet cells [7][8][9][10][11][12]. Moreover, changes in the levels of many miRNAs, including miR-9, miR...

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MicroRNAs as pharmacological targets in diabetes

Cited by 72 publications

References 151 publications

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells

Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells

The emerging role of epigenetics in cardiovascular disease

Therapeutic potential of miRNAs in diabetes mellitus

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