MicroRNA expression profiles of human iPSCs differentiation into insulin-producing cells

Sebastiani, Guido; Valentini, Marco; Grieco, Giuseppina Emanuela; Ventriglia, Giuliana; Nigi, Laura; Mancarella, Francesca; Pellegrini, Silvia; Martino, Gianvito; Sordi, Valeria; Piemonti, Lorenzo; Dotta, Francesco

doi:10.1007/s00592-016-0955-9

Cited by 40 publications

(30 citation statements)

References 46 publications

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“…Multiple studies have shown that miRNAs are pivotal regulators of different aspects of glucose homeostasis, such as peripheral insulin signaling [4], β cells function [5], and phenotype maintenance [6,7].…”

Section: Introductionmentioning

confidence: 99%

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Grieco

Brusco

Licata

et al. 2019

IJMS

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Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia as a consequence of pancreatic β cell loss and/or dysfunction, also caused by oxidative stress. The molecular mechanisms involved inβ cell dysfunction and in response to oxidative stress are also regulated by microRNAs (miRNAs). miRNAs are a class of negative gene regulators, which modulate pathologic mechanisms occurring in diabetes and its complications. Although several pharmacological therapies specifically targeting miRNAs have already been developed and brought to the clinic, most previous miRNA-based drug delivery methods were unable to target a specific miRNA in a single cell type or tissue, leading to important off-target effects. In order to overcome these issues, aptamers and nanoparticles have been described as non-cytotoxic vehicles for miRNA-based drug delivery. These approaches could represent an innovative way to specifically target and modulate miRNAs involved in oxidative stress in diabetes and its complications. Therefore, the aims of this review are: (i) to report the role of miRNAs involved in oxidative stress in diabetes as promising therapeutic targets; (ii) to shed light onto the new delivery strategies developed to modulate the expression of miRNAs in diseases.

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Section: Introductionmentioning

confidence: 99%

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Grieco

Brusco

Licata

et al. 2019

IJMS

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“…Studies have shown that miR-124a plays an important role in pancreatic endocrine development [13,37], insulin biosynthesis and secretion, and insulin signal transduction [12,15]. Despite these important biological roles, little is known about the regulation of miR-124 biogenesis in the pancreas.…”

Section: Discussionmentioning

confidence: 99%

“…Initially described as a brain-specific miRNA in mammals [9,10], MiR-124a-3p (miR-124a), is also well represented in the mouse pancreatic MIN6 β-cell line [11]. Increasing expression levels of miR-124a have been found during embryonic pancreas development [12] and differentiation of human induced pluripotent stem cells (hiPSCs) into insulin-producing cells [13], indicating its function in pancreatic β cell development. Emerging data suggest that miR-124a is overexpressed in pancreatic islets in humans with T2D compared to that in subjects without diabetes [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

EGF suppresses the expression of miR-124a in pancreatic β cell lines via ETS2 activation through the MEK and PI3K signaling pathways

Yang¹,

Zhu²,

Kong³

et al. 2019

Int. J. Biol. Sci.

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Diabetes mellitus is characterized by pancreatic β cell dysfunction. Previous studies have indicated that epidermal growth factor (EGF) and microRNA-124a (miR-124a) play opposite roles in insulin biosynthesis and secretion by beta cells. However, the underlying mechanisms remain poorly understood. In the present study, we demonstrated that EGF could inhibit miR-124a expression in beta cell lines through downstream signaling pathways, including mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) cascades. Further, the transcription factor ETS2, a member of the ETS (E26 transformation-specific) family, was identified to be responsible for the EGF-mediated suppression of miR-124a expression, which was dependent on ETS2 phosphorylation at threonine 72. Activation of ETS2 decreased miR-124a promoter transcriptional activity through the putative conserved binding sites AGGAANA/TN in three miR-124a promoters located in different chromosomes. Of note, ETS2 played a positive role in regulating beta cell function-related genes, including miR-124a targets, Forkhead box a2 (FOXA2) and Neurogenic differentiation 1 (NEUROD1), which may have partly been through the inhibition of miR-124 expression. Knockdown and overexpression of ETS2 led to the prevention and promotion of insulin biosynthesis respectively, while barely affecting the secretion ability. These results suggest that EGF may induce the activation of ETS2 to inhibit miR-124a expression to maintain proper beta cell functions and that ETS2, as a novel regulator of insulin production, is a potential therapeutic target for diabetes mellitus treatment.

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“…16 Pankreas farklılaşması esnasında insan uyarılmış pluripotent kök hücrelerinin insülin üreten hücrelere dönüşmesinde 18 farklı miRNA arasında sadece 347/768 miRNA'larının, belli bir zamanda tüm örneklerde ortak ekspresyon sergilediği bildirilmiştir. 49 Beta hücresine özgü çeşitli miRNA'ların diyabet öncesinde dolaşımda birikmesi, bu moleküllerin teşhiste önemli olabileceğini düşündürmektedir. Pankreas adacıklarında miRNA işlemlerinin düzenlenmesi diyabet durumunda değişmektedir.…”

Section: Di̇yabet Hastaliğinda Pankreati̇k Beta Hücresi̇ Ve Mirna'larunclassified

Type 1 and Type 2 Diabetes-Associated miRNAs

Bolkent¹

2018

Turkiye Klinikleri J Med Sci

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Recent studies have demonstrated the association between miRNAs and the processes of insulin production and secretion in beta cells of endocrine pancreas. miRNAs also play important roles in differentiation, proliferation, and survival of pancreatic beta cells. This review brings together up-to-date knowledge about miRNAs and their role as potential biomarkers in pro-diagnosis, prognosis and treatment of T1D and T2D. miRNA-mediated modulation of gene expression in T1D and T2D is also presented in detail.

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MicroRNA expression profiles of human iPSCs differentiation into insulin-producing cells

Abstract: We detected a specific hiPSCs microRNAs signature during differentiation into insulin-producing cells and demonstrated that differentially expressed microRNAs target several genes involved in pancreas organogenesis.

Cited by 40 publications

References 46 publications

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

Targeting microRNAs as a Therapeutic Strategy to Reduce Oxidative Stress in Diabetes

EGF suppresses the expression of miR-124a in pancreatic β cell lines via ETS2 activation through the MEK and PI3K signaling pathways

Type 1 and Type 2 Diabetes-Associated miRNAs

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