MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion

Sebastiani, Guido; Pò, Agnese; Miele, Evelina; Ventriglia, Giuliana; Ceccarelli, Elena; Bugliani, Marco; Marselli, Lorella; Marchetti, Piero; Gulino, Alberto; Ferretti, Elisabetta; Dotta, Francesco

doi:10.1007/s00592-014-0675-y

Cited by 131 publications

(125 citation statements)

References 38 publications

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“…In fact, an increase in the level of pre-miR-375 has been reported in GK rats [26] but this observation was not confirmed by an independent study [30]. A small elevation of miR-375 was also reported in islets of ob/ob and DIO mice [18,29], but changes in miR-375 expression were neither detected in other studies by microarray profiling of islets of ob/ob, db/db and DIO mice [31,32] nor in islets of T2DM human donors [21,33]. Interestingly, increased levels of miR-375 were observed in the islets of the offspring of rats fed a low-protein diet during pregnancy.…”

Section: Role Of Specific Mirnas In the Development Of β-Cells And Inmentioning

confidence: 58%

“…In the same study, miR-21 was found to be significantly upregulated and miR-127-3p and miR-375 had a tendency to be more elevated in islets of glucose intolerant donors [51]. In other independent studies, expression of miR-375 was found to be increased in total pancreas [52] but not in isolated pancreatic islets of T2DM donors [33]. Two other miRNAs, miR-187 and miR-124a, were found to be upregulated in islets of individuals suffering from T2DM, whereas miR-7 and miR-184 were down-regulated [18,33,39,53].…”

Section: Mirna Changes In Islets Of Human T2dm Donorsmentioning

confidence: 67%

“…In other independent studies, expression of miR-375 was found to be increased in total pancreas [52] but not in isolated pancreatic islets of T2DM donors [33]. Two other miRNAs, miR-187 and miR-124a, were found to be upregulated in islets of individuals suffering from T2DM, whereas miR-7 and miR-184 were down-regulated [18,33,39,53]. Overexpression of both miR-187 and miR124a was linked in in vitro rodent models to a reduction in glucose-induced insulin secretion by directly targeting HIPK3 or Rab27A, Mtpn and Foxa2, respectively [33,[53][54][55].…”

Section: Mirna Changes In Islets Of Human T2dm Donorsmentioning

confidence: 99%

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MicroRNAs and the functional β cell mass: For better or worse

Guay

Regazzi

2015

Diabetes & Metabolism

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Insulin secretion from pancreatic β-cells plays a central role in the control of blood glucose levels. The amount of insulin released by β-cells is precisely adjusted to match the organism requirements. A number of conditions occurring during life, including pregnancy and obesity, can result in a decrease in the sensitivity of insulin target tissues and in the consequent rise in the insulin needs. To preserve glucose homeostasis, the augmented insulin demand requires a compensatory expansion of the mass of pancreatic β-cells and an increase in their secretory activity. This compensatory process is known to be accompanied by modifications in β-cell gene expression but the molecular mechanisms underlying this phenomenon are still poorly understood. Emerging evidence indicate that at least part of these compensatory events may be orchestrated by changes in the level of a novel class of gene regulators, the microRNAs.Indeed, several of these small non-coding RNAs have either positive or negative impacts on β-cell proliferation and survival. The studies reviewed in this paper suggest that the balance between the actions of these two groups of microRNAs with opposing functional effects determines whether β-cells expand sufficiently to maintain blood glucose levels in the normal range or fail to meet the insulin demand with a consequent progression toward diabetes manifestation. A better understanding of the mechanisms governing the changes in the microRNA profile will open the way for the development of new strategies to prevent and/or treat type 2 and gestational diabetes.

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Section: Role Of Specific Mirnas In the Development Of β-Cells And Inmentioning

confidence: 58%

Section: Mirna Changes In Islets Of Human T2dm Donorsmentioning

confidence: 67%

Section: Mirna Changes In Islets Of Human T2dm Donorsmentioning

confidence: 99%

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MicroRNAs and the functional β cell mass: For better or worse

Guay

Regazzi

2015

Diabetes & Metabolism

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“…In pancreatic islets from T2D donors, miR124a was expressed at much higher levels compared to normal islets [54]. Overexpression of miR124a in MIN6 cells resulted in impaired glucosestimulated insulin secretion and silencing of this miRNA correlated with increased expression of predicted target genes of relevance to β-cell function, including Mtpn, Foxa2, Flot2, Akt3, Sirt1, and NeuroD1.…”

Section: Mirnas Involved In the Regulation Of Pancreatic β-Cell Functionmentioning

confidence: 99%

“…In humans, several studies have shown that miR-375 is upregulated in the pancreas or plasma of patients with T2D compared to non-diabetic individuals [51][52][53], while others found no evidence for differential expression [54] or observed decreased expression levels in individuals with impaired glucose tolerance [55]. Altered miR-375 expression has been correlated with changes in methylation status of its promoter [51,52,55].…”

Section: Mirnas Involved In the Regulation Of Pancreatic β-Cell Functionmentioning

confidence: 99%

Beyond the Protein-Coding Sequence: Noncoding RNAs in the Pathogenesis of Type 2 Diabetes

DiStefano¹

2015

Rev Diabet Stud

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■ AbstractDiabetes mellitus results from a deficiency or failure to maintain normal glucose homeostasis. The most common form of the disease is type 2 diabetes (T2D), a progressive metabolic disorder characterized by elevated glucose levels that develops in response to either multi-organ insulin resistance or insufficient insulin secretion from pancreatic β-cells. Although the etiology of T2D is complex, many factors are known to contribute to defects of glucose homeostasis, including obesity, unhealthy lifestyle choices, genetic susceptibility, and environmental exposures. In addition to these factors, noncoding RNAs (ncRNAs) have been recently implicated in the pathogenesis of T2D, playing roles in several of the pathophysiological mechanisms underlying the disease, particularly in insulin-sensitive tissues such as pancreatic β-cells, liver, muscle, and adipose tissue. A growing number of publications demonstrate that polymorphisms in ncRNAs or their target genes may represent a new class of genetic variation contributing to the development of T2D. This review summarizes both the current state of knowledge of ncRNAs, specifically microRNAs (miRNAs), involved in the regulation of β-cell function, insulin sensitivity, and insulin action in peripheral organs. The role of genetic variation in miRNAs or miRNA binding sites in the pathogenesis of T2D is also discussed. While far less is known about the impact of long ncRNAs (lncRNAs) in the development of T2D, emerging evidence suggests that these molecules may be able to contribute to β-cell dysfunction in response to hyperglycemia. This article provides an overview of the studies conducted to date in this field, focusing on lncRNAs that are dysregulated in human pancreatic islets.

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MicroRNA‐124: An emerging therapeutic target in cancer

et al. 2019

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MicroRNAs (miRNAs) are noncoding single‐stranded RNAs, approximately 20‐24 nucleotides in length, known as powerful posttranscriptional regulators. miRNAs play important regulatory roles in cellular processes by changing messenger RNA expression and are widely involved in human diseases, including tumors. It has been reported in the literature that miRNAs have a precise role in cell proliferation, programmed cell death, differentiation, and expression of coding genes. MicroRNA‐124 (miR‐124) has reduced exparession in various human neoplasms and is believed to be related to the occurrence, development, and prognosis of malignant tumors. In our review, we focus on the specific molecular functions of miR‐124 and the downstream gene targets in major cancers, which provide preclinical evidence for the treatment of human cancer. Although some obstacles exist, miR‐124 is still attracting intensive research focus as a promising and effective anticancer weapon.

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MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion

Cited by 131 publications

References 38 publications

MicroRNAs and the functional β cell mass: For better or worse

MicroRNAs and the functional β cell mass: For better or worse

Beyond the Protein-Coding Sequence: Noncoding RNAs in the Pathogenesis of Type 2 Diabetes

MicroRNA‐124: An emerging therapeutic target in cancer

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