miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate gestational diabetes mellitus

Mi, Yang; Guo, Na; He, Tongqiang; Ji, Jing; Li, Zhibin; Huang, Pu

doi:10.1530/jme-15-0100

Cited by 17 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell culture experiments under normoxia and hypoxia conditions can elucidate the studies of EVs in vivo after acute exercise. In cell culture experiments, cardiomyocytes increased EVs release under hypoxia environment ( MacPherson et al, 2015 ; Mi et al, 2015 ). Therefore, part of the augmented concentration of EVs in rat serum after exercise could be a consequence of the reduction in the oxygen supply at the tissue level.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute Aerobic Exercise on Rats Serum Extracellular Vesicles Diameter, Concentration and Small RNAs Content

et al. 2018

View full text Add to dashboard Cite

Physical exercise stimulates organs, mainly the skeletal muscle, to release a broad range of molecules, recently dubbed exerkines. Among them, RNAs, such as miRNAs, piRNAs, and tRNAs loaded in extracellular vesicles (EVs) have the potential to play a significant role in the way muscle and other organs communicate to translate exercise into health. Low, moderate and high intensity treadmill protocols were applied to rat groups, aiming to investigate the impact of exercise on serum EVs and their associated small RNA molecules. Transmission electron microscopy, resistive pulse sensing, and western blotting were used to investigate EVs morphology, size distribution, concentration and EVs marker proteins. Small RNA libraries from EVs RNA were sequenced. Exercise did not change EVs size, while increased EVs concentration. Twelve miRNAs were found differentially expressed after exercise: rno-miR-128-3p, 103-3p, 330-5p, 148a-3p, 191a-5p, 10b-5p, 93-5p, 25-3p, 142-5p, 3068-3p, 142-3p, and 410-3p. No piRNA was found differentially expressed, and one tRNA, trna8336, was found down-regulated after exercise. The differentially expressed miRNAs were predicted to target genes involved in the MAPK pathway. A single bout of exercise impacts EVs and their small RNA load, reinforcing the need for a more detailed investigation into EVs and their load as mediators of health-promoting exercise.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Acute Aerobic Exercise on Rats Serum Extracellular Vesicles Diameter, Concentration and Small RNAs Content

et al. 2018

View full text Add to dashboard Cite

show abstract

“…It was recently demonstrated that miR-347a directly target LDHA in colorectal cancer cells [60]. MiR-410 represses LDHA expression and promotes embryonic stem cells (hESC) to differentiate into pancreatic endoderm (PE) in gestational diabetes mellitus treatment [61]. In our study, we showed that miR-34b-3 and miR-449a directly targeted LDHA and LDHA overexpression significantly recovered cell proliferation, LD content and LDH activity in NPC cells following transfection of miR-34b-3 and miR-449a.…”

Section: Discussionmentioning

confidence: 99%

MiR-34b-3 and miR-449a inhibit malignant progression of nasopharyngeal carcinoma by targeting lactate dehydrogenase A

et al. 2016

Oncotarget

View full text Add to dashboard Cite

MicroRNA expression profiling assays have shown that miR-34b/c and miR-449a are down-regulated in nasopharyngeal carcinoma (NPC); however, the targets and functions of miR-34b/c and miR-449a in the pathologenesis of NPC remain elusive. In this study, we verified miR-34b/c and miR-449a were significantly reduced with the advance of NPC. Overexpression of miR-34b-3 and miR-449a suppressed the growth of NPC cells in culture and mouse tumor xenografts. Using tandem mass tags for quantitative labeling and LC-MS/MS analysis to investigate protein changes after restoring expression of miR-34b-3, 251 proteins were found to be down-regulated after miR-34b-3 transfection. Through 3 replicate experiments, we found that miR-34b-3 regulated the expression of 15 potential targeted genes mainly clustered in the key enzymes of glycolysis metabolism, including lactate dehydrogenase A (LDHA). Further investigation revealed that miR-34b-3 and miR-449a negatively regulated LDHA by binding to the 3′ untranslated regions of LDHA. Furthermore, LDHA overexpression rescued the miR-34b-3 and miR-449a induced tumor inhibition effect in CNE2 cells. In addition, miR-34b-3 and miR-449a suppressed LDH activity and reduced LD content, which were directly induced by downregulation of the LDHA. Our findings suggest that miR-34b-3 and miR-449a suppress the development of NPC through regulation of glycolysis via targeting LDHA and may be potential therapeutic targets for the treatment of NPC.

show abstract

“…Overexpression of miR-186 and miR-375 by chemical transfection of human iPSCs promoted islet-like cell cluster formation and induced β-cell lineage markers [113] . Furthermore, human embryonic stem cells with induced overexpression of miR-410 and miR-495, prior to differentiation into endoderm, led to improved glycemic control when transplanted in mouse models of gestational or T2D [114] , [115] . These studies demonstrate that miRNAs can direct developmental decisions and promote differentiation of distinct cell lineages and may be exploited therapeutically in stem-cell-based approaches aiming to replace differentiated endocrine cells for the treatment of diabetes.…”

Section: Mirna Therapeuticsmentioning

confidence: 99%

MicroRNAs as stress regulators in pancreatic beta cells and diabetes

LaPierre¹,

Stoffel²

2017

Molecular Metabolism

140

120

View full text Add to dashboard Cite

BackgroundMicroRNAs have emerged as important regulatory non-coding RNAs that tune cellular responses to physiological perturbations and disease conditions. An increasing body of literature underlines the important roles of miRNA function in pancreatic β-cells in response to metabolic, genetic and inflammatory stress. Lessons from genetic loss- and gain-of-function studies have implicated several highly expressed and evolutionary conserved miRNAs in stress signal modulation, resolution and buffering, thereby forming stabilizing miRNA networks that preserve β-cell differentiation, function, proliferation and cell survival.Scope of ReviewThis review will summarize our current knowledge of how biologically relevant miRNAs regulate stress responses in pancreatic β-cells, discuss the challenges and opportunities associated with using secreted miRNAs as biomarkers and forecast how mechanistic knowledge of miRNA function can be exploited in developing miRNA-based therapeutics.Major ConclusionsmiRNAs play important roles in the function, differentiation, proliferation, and survival of pancreatic β-cells. Many miRNA families that are regulated by metabolic, genetic, and inflammatory stressors have been found to coordinate the adaptive responses of β-cells in vivo in conditions such as obesity and diabetes.

show abstract

miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate gestational diabetes mellitus

Cited by 17 publications

References 36 publications

Effects of Acute Aerobic Exercise on Rats Serum Extracellular Vesicles Diameter, Concentration and Small RNAs Content

Effects of Acute Aerobic Exercise on Rats Serum Extracellular Vesicles Diameter, Concentration and Small RNAs Content

MiR-34b-3 and miR-449a inhibit malignant progression of nasopharyngeal carcinoma by targeting lactate dehydrogenase A

MicroRNAs as stress regulators in pancreatic beta cells and diabetes

Contact Info

Product

Resources

About