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Analysis of potential functional significance of microRNA?3613?3p in human umbilical vein endothelial cells affected by heat stress.

ABSTRACT: Dysregulation of microRNA?3613?3p (miR?3613?3p) was previously reported in endothelial cells (ECs) during heat stress. The aim of the present study was to investigate the precise role of miR?3613?3p in heat stress. In the present study, potential gene targets of miR?3613?3p in heat?treated ECs were assessed, and the potential effects of miR?3613?3p were determined using Gene Ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify signaling pathways that may be affected by miR?3613?3p in heat?treated cells. Reverse transcription?quantitative PCR, western blotting and annexin V?FITC/propidium iodide staining were performed to detect miRNA expression, protein expression and apoptosis, respectively. Luciferase gene reporter assay was performed to evaluate the association between miR?3613?3p and mitogen?activated protein kinase kinase kinase 2 (MAP3K2). Bioinformatics analysis revealed 865 potential gene targets for miR?3613?3p and a series of functions and pathways in heat?treated ECs. 'Negative regulation of apoptotic process' was identified as a potential function of miR?3613?3p. In addition, functional analysis confirmed the downregulated expression levels of miR?3613?3p in ECs during heat stress, which was accompanied by an increase in apoptosis; restoration of miR?3613?3p expression inhibited apoptosis. MAP3K2 protein was demonstrated to be upregulated in heat?treated ECs, and overexpression of miR?3613?3p reduced MAP3K2 expression levels. Additionally, MAP3K2 was targeted by miR?3613?3p. These results indicated that miR?3613?3p may have complicated roles in ECs under heat stress. miR?3613?3p may serve an important role in the apoptosis of heat?treated ECs, and this effect may be partly achieved by targeting MAP3K2.

SUBMITTER: Liu J

PROVIDER: S-EPMC6625459 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Analysis of potential functional significance of microRNA‑3613‑3p in human umbilical vein endothelial cells affected by heat stress.

Liu Jie J Han Xuan X Zhu Guoguo G Liu Shixin S Lu Qiping Q Tang Zhongzhi Z

Molecular medicine reports 20190611 2

Dysregulation of microRNA‑3613‑3p (miR‑3613‑3p) was previously reported in endothelial cells (ECs) during heat stress. The aim of the present study was to investigate the precise role of miR‑3613‑3p in heat stress. In the present study, potential gene targets of miR‑3613‑3p in heat‑treated ECs were assessed, and the potential effects of miR‑3613‑3p were determined using Gene Ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify signaling path ...[more]

PMID: 31257536

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Project description:BackgroundExposure to diabetes in utero influences future metabolic health of the offspring. MicroRNAs (miRNA) are small noncoding RNAs that may contribute mechanistically to the effects on offspring imparted by diabetes mellitus (DM) during pregnancy. We hypothesized that exposure to DM during pregnancy influences select miRNAs in fetal circulation, in human umbilical vein endothelial cells (HUVEC), and placenta.MethodsmiRNA abundance was quantified using real-time PCR from RNA isolated from umbilical cord serum exosomes, HUVEC, and placenta exposed to diabetes or normoglycemia during pregnancy. The abundance of each of these miRNAs was determined by comparison to a known standard and the relative expression assessed using the 2-ΔΔCt method. Multivariable regression models examined the associations between exposure to diabetes during pregnancy and miRNA expression.ResultsmiR-126-3p was highly abundant in fetal circulation, HUVEC, and placenta. Diabetes exposure during pregnancy resulted in lower expression of miR-148a-3p and miR-29a-3p in the HUVEC. In the placenta, for miR-126-3p, there was a differential effect of DM by birth weight between DM versus control group, expression being lower at the lower birth weight, however not different at the higher birth weight.ConclusionExposure to DM during pregnancy alters miRNA expression in the offspring in a tissue-specific manner.ImpactmiRNAs are differentially expressed in fetal tissues from offspring exposed to in utero diabetes mellitus compared to those who were not exposed. miRNA expression differs among tissue types (human umbilical vein endothelial cells, placenta and circulation exosomes) and response to diabetes exposure varies according to tissue of origin. miRNA expression is also affected by maternal and infant characteristics such as infant birth weight, infant sex, maternal age, and maternal BMI. miRNAs might be one of the potential mechanisms by which offspring's future metabolic status may be influenced by maternal diabetes mellitus.

Dataset Information

Analysis of potential functional significance of microRNA?3613?3p in human umbilical vein endothelial cells affected by heat stress.

Publications

Analysis of potential functional significance of microRNA‑3613‑3p in human umbilical vein endothelial cells affected by heat stress.

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