A pancreatic islet-specific microRNA regulates insulin secretion

Poy, Matthew N.; Eliasson, Lena; Krützfeldt, Jan; Kuwajima, Satoru; Ma, Xiaosong; MacDonald, Patrick E.; Pfeffer, Sébastien; Tuschl, Thomas; Rajewsky, Nikolaus; Rorsman, Patrik; Stoffel, Markus

doi:10.1038/nature03076

Cited by 1,914 publications

(1,579 citation statements)

References 29 publications

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“…MiRNAs play important roles in the development, differentiation, metabolism, cell growth and death in animals and plants (Poy et al, 2004;Cheng et al, 2005;Dresios et al, 2005). There is also evidence that supports a role for miRNAs in hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Garzon¹,

Pichiorri²,

et al. 2007

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MicroRNAs (miRNAs) are small non-coding RNAs of 19-25 nucleotides that are involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. However, little is known about the role of miRNAs in granulopoiesis. Here, we report the expression of miRNAs in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid (ATRA) treatment by using a miRNA microarrays platform and quantitative real time-polymerase chain reaction (qRT-PCR). We found upregulation of miR-15a, miR-15b, miR-16-1, let-7a-3, let-7c, let-7d, miR-223, miR-342 and miR-107, whereas miR-181b was downregulated. Among the upregulated miRNAs, miR-107 is predicted to target NFI-A, a gene that has been involved in a regulatory loop involving miR-223 and C/EBPa during granulocytic differentiation. Indeed, we have confirmed that miR-107 targets NF1-A. To get insights about ATRA regulation of miRNAs, we searched for ATRA-modulated transcription factors binding sites in the upstream genomic region of the let-7a-3/let-7b cluster and identified several putative nuclear factor-kappa B (NF-jB) consensus elements. The use of reporter gene assays, chromatin immunoprecipitation and site-directed mutagenesis revealed that one proximal NF-jB binding site is essential for the transactivation of the let-7a-3/let-7b cluster. Finally, we show that ATRA downregulation of RAS and Bcl2 correlate with the activation of known miRNA regulators of those proteins, let-7a and miR-15a/ miR-16-1, respectively.

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Section: Introductionmentioning

confidence: 99%

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Garzon¹,

Pichiorri²,

et al. 2007

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“…The initial paper reporting the first cloning effort of miRNAs in the pancreatic β-cell identified 67 unique sequences including miR-375 [5]. As current sequencing technologies have long rendered this cloning method obsolete, they have also revealed the potential for hundreds of unique functional sequences to be present in most cell types including the β-cell.…”

Section: Microrna Profiling In the Pancreatic β-Cell And Isletsmentioning

confidence: 99%

“…The chronic hyperglycemia characteristic of diabetes has long been established the result of inadequate insulin action making one of the prime directives of the β-cell field to identify genes and mechanisms which contribute to reduced growth and function of this cell type. Since the first gain and loss of function studies on miR-375, several subsequent reports have identified a number of additional miRNAs as negative regulators of β-cell function including miR-7, miR-184, miR-21, miR-29a and miR-33a [5] [12] [8] [17] [18]. Importantly, the role of several miRNAs as negative regulators has been substantiated using specific genetic mouse knockouts [19].…”

Section: Microrna Profiling In the Pancreatic β-Cell And Isletsmentioning

confidence: 99%

MicroRNAs: An adaptive mechanism in the pancreatic β-cell…and beyond?

Poy

2016

Best Practice & Research Clinical Endocrinology & Metab

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Recent protocols have been developed to differentiate human stem cells and fibroblasts into insulin-producing cells capable of releasing the hormone in a glucosestimulated manner. Limitations remain which prevent bringing these protocols to a clinical setting as these models must still undergo complete characterization. Advances in sequencing technologies have driven the identification of several noncoding RNA species including microRNAs (miRNAs). While their diversity and unique expression patterns across different tissues have made deciphering their precise functional role a significant challenge, studies using both cell lines and transgenic mouse models have made substantial progress in understanding their regulatory role on exocytosis and proliferation of the β-cell. These results also indicate miRNAs play an integral role in the fundamental mechanics of how the cell manages the balance between these independent functions. Continued investigation into miRNA function may uncover mechanisms which can be exploited to improve differentiation protocols in producing fully mature β-cells.

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“…Regardless of the deficiency in three different hormones in df/df mice, GH seems to be a main regulator of lifespan in healthy animals. These hormonal alterations may play important role in the patterns of circulating miRNAs reported in the present study, as it has been previously shown that groups of miRNA may regulate or are regulated by endocrine signals (Poy et al ., 2004). We previously showed altered patterns and regulations of liver miRNA in Ames dwarf mice (Bates et al ., 2010); however, in the present study we examined circulating miRNA in young and old df/df and normal mice.…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

et al. 2015

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SummaryRecent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long‐lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype‐specific changes in the circulating levels of 21 miRNAs during aging [genotype‐by‐age interaction (GbA)]. Genotype‐by‐age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age‐related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti‐inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long‐lived mouse suggests CR‐like and CR‐independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long‐lived Ames mouse.

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A pancreatic islet-specific microRNA regulates insulin secretion

Cited by 1,914 publications

References 29 publications

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

MicroRNAs: An adaptive mechanism in the pancreatic β-cell…and beyond?

Circulating microRNA signature of genotype‐by‐age interactions in the long‐lived Ames dwarf mouse

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