Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

Ferland-McCollough, David; Fernandez‐Twinn, Denise S.; Cannell, Ian G.; David, Hansi Priscilla; Warner, Matthew J.; Vaag, Allan; Bork-Jensen, Jette; Brøns, Charlotte; Gant, Timothy W.; Willis, Anne E.; Siddle, Kenneth; Bushell, Martin; Ozanne, Susan E.

doi:10.1038/cdd.2011.183

Cited by 136 publications

(128 citation statements)

References 40 publications

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“…13 Additional miR-483-3p target genes including BBC3/ PUMA, SMAD4, CTNNB1 and GDF3 have been identified in other tissues (Wilm's tumors, adrenocortical carcinomas, HCT116 colon and HepG2 hepatocellular carcinoma cell lines, and adipose tissue). [14][15][16][17][18] We demonstrate now that CDC25A has a key role in the mediation of the anti-proliferative effects of miR-483-3p in keratinocytes by controlling the binding between CDK6/4 and CCNDs. Our results obtained on CDK6 shed new light on the mechanisms that control CCND-CDK6/4 assembly in early G1, showing that this association greatly depends on the phosphorylation status of the Y residues located in the 'Glycin rich domain' of these kinases.…”

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confidence: 64%

CDC25A targeting by miR-483-3p decreases CCND–CDK4/6 assembly and contributes to cell cycle arrest

et al. 2013

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Disruption of contact inhibition and serum afflux that occur after a tissue injury activate cell cycle, which then stops when confluence is reached again. Although the events involved in cell cycle entry have been widely documented, those managing cell cycle exit have remained so far ill defined. We have identified that the final stage of wound closure is preceded in keratinocytes by a strong accumulation of miR-483-3p, which acts as a mandatory signal triggering cell cycle arrest when confluence is reached. Blocking miR-483-3p accumulation strongly delays cell cycle exit, maintains cells into a proliferative state and retards their differentiation program. Using two models of cell cycle synchronization (i.e. mechanical injury and serum addition), we show that an ectopic upregulation of miR-483-3p blocks cell cycle progression in early G1 phase. This arrest results from a direct targeting of the CDC25A phosphatase by miR-483-3p, which can be impeded using an anti-miRNA against miR-483-3p or a protector that blocks the complex formation between miR-483-3p and the 3 0 -untranslated region (UTR) of CDC25A transcript. We show that the miRNA-induced silencing of CDC25A increases the tyrosine phosphorylation status of CDK4/6 cyclin-dependent kinases which, in turn, abolishes CDK4/6 capacity to associate with D-type cyclins. This prevents CDK4/6 kinases' activation, impairs downstream events such as cyclin E stimulation and sequesters cells in early G1. We propose this new regulatory process of cyclin-CDK association as a general mechanism coupling miRNA-mediated CDC25A invalidation to CDK posttranscriptional modifications and cell cycle control.

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confidence: 64%

CDC25A targeting by miR-483-3p decreases CCND–CDK4/6 assembly and contributes to cell cycle arrest

et al. 2013

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“…There is now accumulating evidence that translational repression of miRNA targets is the primary event in the mechanism; several groups have demonstrated that repression can be seen without the necessity for mRNA degradation. [58][59][60][61][62][63][64][65] In vitro studies showed that miRNA-mediated repression is a two-step process, the first of which affects translation of the target mRNA. 59,66 These were followed by a series of reports that employed temporal studies to demonstrate that translational repression of miRNA targets precedes deadenylation and degradation in Drosophila, zebrafish and mammalian cells.…”

Section: Steps To Repressionmentioning

confidence: 99%

The complexity of miRNA-mediated repression

2014

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Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (B22 nt) non-coding RNA molecules are highly conserved in evolution and are present in nearly all eukaryotes. They have critical roles in virtually every cellular process, particularly determination of cell fate in development and regulation of the cell cycle. Although it has long been known that miRNAs bind to mRNAs to trigger translational repression and degradation, there had been much debate regarding their precise mode of action. It is now believed that translational control is the primary event, only later followed by mRNA destabilisation. This review will discuss the most recent advances in our understanding of the molecular underpinnings of miRNA-mediated repression. Moreover, we highlight the multitude of regulatory mechanisms that modulate miRNA function.

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“…Furthermore, nutrient-dependent modulation of microRNAs (miRNAs) may also trigger disease susceptibility and metabolic complications in offspring. Indeed, misexpressed miRNAs participate in the programming of adipose tissue in rats with retarded growth, causing lipotoxicity and insulin resistance, and hence they increase the susceptibility to metabolic disease during adulthood (10).…”

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confidence: 99%

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

et al. 2014

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The intrauterine environment of the fetus is a preeminent actor in long-term health. Indeed, mounting evidence shows that maternal malnutrition increases the risk of type 2 diabetes (T2D) in progeny. Although the consequences of a disturbed prenatal environment on the development of the pancreas are known, the underlying mechanisms are poorly defined. In rats, restriction of protein during gestation alters the development of the endocrine pancreas and favors the occurrence of T2D later in life. Here we evaluate the potential role of perturbed microRNA (miRNA) expression in the decreased b-cell mass and insulin secretion characterizing progeny of pregnant dams fed a low-protein (LP) diet. miRNA profiling shows increased expression of several miRNAs, including miR-375, in the pancreas of fetuses of mothers fed an LP diet. The expression of miR-375 remains augmented in neoformed islets derived from fetuses and in islets from adult (3-month-old) progeny of mothers fed an LP diet. miR-375 regulates the proliferation and insulin secretion of dissociated islet cells, contributing to the reduced b-cell mass and function of progeny of mothers fed an LP diet. Remarkably, miR-375 normalization in LP-derived islet cells restores b-cell proliferation and insulin secretion. Our findings suggest the existence of a developmental memory in islets that registers intrauterine protein restriction. Hence, pancreatic failure after in utero malnutrition could result from transgenerational transmission of miRNA misexpression in b-cells.

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Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

Cited by 136 publications

References 40 publications

CDC25A targeting by miR-483-3p decreases CCND–CDK4/6 assembly and contributes to cell cycle arrest

CDC25A targeting by miR-483-3p decreases CCND–CDK4/6 assembly and contributes to cell cycle arrest

The complexity of miRNA-mediated repression

Maternal Protein Restriction Leads to Pancreatic Failure in Offspring: Role of Misexpressed MicroRNA-375

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