Therapeutic potential of miRNAs in diabetes mellitus

Abstract

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...

Involvement of Epigenetics in the Pathogenesis, Testing and Management of Coronavirus Disease 2019 (COVID-19) Pandemic: A Narrative Review

“…For COVID-19 induced by the overexpression of viral miRNAs due to hypermethylation, complementary single-stranded oligonucleotides otherwise called anti-miRNAs can be used to suppress the virus's infectivity [43]. The hypomethylation of the host miRNAs makes it to be susceptible to SARS-CoV-2; it can also be normalized by adding RNA molecules analogous to the precursors of the target miRNA or adding oligonucleotides that mimic the mature form of the miRNA of interest [44]. Some proven anti-miRNAs include Locked Nucleic Acid (LNA), antagomirs, morpholinos, byetta, victoza, trulicity, janu-via, onglyza, and tradjenta [45][46][47].…”