Embryonic stem cell-derived pancreatic endoderm transplant with MCT1-suppressing miR-495 attenuates type II diabetes in mice

Liang, Dong; Zhang, Yang; Han, Jun; Wang, Wei; Liu, Yin; Li, Junfeng; Jiang, Xia

doi:10.1507/endocrj.ej15-0186

Cited by 25 publications

(16 citation statements)

References 39 publications

(35 reference statements)

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“…Glu, glucose; Pyr, pyruvate; Lac, lactate; Glut, glutamante; Orn, ornitine; PolII, RNA polymerase II; Mito, mitochondria. Data source: Pullen et al (2011), Klein et al (2013), Liang et al (2015), Martinez-Sanchez et al (2015), Tugay et al (2016). See the main text for further details.…”

Section: Mirnas and Disallowed Genesmentioning

confidence: 99%

“…Although, this gene is regulated by miR-124 in medulloblastomas (Li et al, 2009), miR-124 is not expressed at significant levels in mouse islets, at least in young adults, and is thus unlikely to impact Slc16a1 expression in β-cells at this developmental stage (Pullen et al, 2011). More recently, Liang et al (2015) showed that miR-495 targets Slc16a1 in human embryonic stem cell (hESC) derived pancreatic endoderm that improved T2D symptoms upon transplantation in a murine model for T2D.…”

Section: Mirnas and Disallowed Genesmentioning

confidence: 99%

“…Virus-mediated overexpression of miR-375 in human skin fibroblast-derived iPSCs is sufficient to trigger their differentiation into insulin-expressing cells and allow glucose-dependent insulin secretion in vitro (Lahmy et al, 2014). Finally, hESCs overexpressing miR-410, miR-495, and miR-590 that have subsequently been subjected to differentiation into endoderm can improved glycemic control when transplanted in mouse models of gestational or T2D diabetes (Chen et al, 2015; Liang et al, 2015; Mi et al, 2015). Interestingly, Ldha and Mct1/Slc16a1, two disallowed genes in β-cells, are repressed by these miRNAs in hESCs (Chen et al, 2015; Liang et al, 2015; Mi et al, 2015), demonstrating that miRNA-mediated regulation of disallowed genes is also of functional importance during the differentiation of pluripotent cells into β-cells.…”

Section: Perspectives For Future Studymentioning

confidence: 99%

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MiRNAs in β-Cell Development, Identity, and Disease

2017

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Pancreatic β-cells regulate glucose metabolism by secreting insulin, which in turn stimulates the utilization or storage of the sugar by peripheral tissues. Insulin insufficiency and a prolonged period of insulin resistance are usually the core components of type 2 diabetes (T2D). Although, decreased insulin levels in T2D have long been attributed to a decrease in β-cell function and/or mass, this model has recently been refined with the recognition that a loss of β-cell “identity” and dedifferentiation also contribute to the decline in insulin production. MicroRNAs (miRNAs) are key regulatory molecules that display tissue-specific expression patterns and maintain the differentiated state of somatic cells. During the past few years, great strides have been made in understanding how miRNA circuits impact β-cell identity. Here, we review current knowledge on the role of miRNAs in regulating the acquisition of the β-cell fate during development and in maintaining mature β-cell identity and function during stress situations such as obesity, pregnancy, aging, or diabetes. We also discuss how miRNA function could be harnessed to improve our ability to generate β-cells for replacement therapy for T2D.

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Section: Mirnas and Disallowed Genesmentioning

confidence: 99%

Section: Mirnas and Disallowed Genesmentioning

confidence: 99%

Section: Perspectives For Future Studymentioning

confidence: 99%

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MiRNAs in β-Cell Development, Identity, and Disease

2017

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“…miR‐495 is involved in type II diabetes in mice . In addition, miR‐495 participates in the pathogenesis of cancer .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐495 regulates starvation‐induced autophagy by targeting ATG3

Yang

Hou

et al. 2016

FEBS Letters

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The functions of some essential autophagy genes are regulated by microRNAs. However, an ATG3-modulating microRNA has never been reported. Here we show that the transcription of miR-495 negatively correlates with the translation of ATG3 under nutrient-deprived or rapamycin-treated conditions. miR-495 targets ATG3 and regulates its protein levels under starvation conditions. miR-495 also inhibits starvation-induced autophagy by decreasing the number of autophagosomes and by preventing LC3-I-to-LC3-II transition and P62 degradation. These processes are reversed by the overexpression of an endogenous miR-495 inhibitor. Re-expression of Atg3 without miR-495 response elements restores miR-495-inhibited autophagy. miR-495 sustains cell viability under starvation conditions but has no effect under hypoxia. Moreover, miR-495 inhibits etoposide-induced cell death. In conclusion, miR-495 is involved in starvation-induced autophagy by regulating Atg3.

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“…In the same way as LDH enzymes, lactate carriers (MCT proteins) are regulated by diverse miRNAs. For example, MCT1 is targeted by miR-29a, miR-29b, miR-124, and miR-495 in pancreatic β cells (101,102). Another MCT1regulatory miRNA is miR-342-3p, which promotes alterations in lactate and glucose flows.…”

Section: Mirnas Involved In Lactate Metabolismmentioning

confidence: 99%

MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities

et al. 2019

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Dysregulated metabolism is a common feature of cancer cells and is considered a hallmark of cancer. Altered tumor-metabolism confers an adaptive advantage to cancer cells to fulfill the high energetic requirements for the maintenance of high proliferation rates, similarly, reprogramming metabolism confers the ability to grow at low oxygen concentrations and to use alternative carbon sources. These phenomena result from the dysregulated expression of diverse genes, including those encoding microRNAs (miRNAs) which are involved in several metabolic and tumorigenic pathways through its post-transcriptional-regulatory activity. Further, the identification of key actionable altered miRNA has allowed to propose novel targeted therapies to modulated tumor-metabolism. In this review, we discussed the different roles of miRNAs in cancer cell metabolism and novel miRNA-based strategies designed to target the metabolic machinery in human cancer.

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Embryonic stem cell-derived pancreatic endoderm transplant with MCT1-suppressing miR-495 attenuates type II diabetes in mice

Cited by 25 publications

References 39 publications

MiRNAs in β-Cell Development, Identity, and Disease

MiRNAs in β-Cell Development, Identity, and Disease

MicroRNA‐495 regulates starvation‐induced autophagy by targeting ATG3

MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities

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