Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome

Raitoharju, Emma; Seppälä, Ilkka; Oksala, Niku; Lyytikäinen, Leo-Pekka; Raitakari, Olli T.; Viikari, Jorma; Ala‐Korpela, Mika; Soininen, Pasi; Kangas, Antti J.; Waldenberger, Mélanie; Klopp, Norman; Illig, Thomas; Leiviskä, Jaana; Loo, Britt-Marie; Hutri‐Kähönen, Nina; Kähönen, Mika; Laaksonen, Reijo; Lehtimäki, Terho

doi:10.1016/j.mce.2014.04.013

Cited by 69 publications

(67 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The research of de Bruind et al showed that PIK3R3 could affect insulin resistance via the IGF-1 signaling pathway [24]. In addition, hsa-miR-144 was also confirmed to downregulate the expression of insulin receptors, hinder the uptake of glucose, and delay the progression of insulin signaling [25]. In our study, this miRNA targeted several genes including GRM5 , ARPC4 , APP , and FAT4 .…”

Section: Discussionsupporting

confidence: 64%

Comparison of Transcriptome Between Type 2 Diabetes Mellitus and Impaired Fasting Glucose

Cui

Chi

et al. 2016

Med Sci Monit

View full text Add to dashboard Cite

BackgroundThe aim of this study was to compare the transcriptome between impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and further research their molecular mechanisms.Material/MethodsThe original microarray GSE21321, including miRNA and mRNA expression profiles, was downloaded from the GEO database. Data preprocessing was processed by limma package, and differentially expressed genes (DGs) and miRNA (DMs) were screened. Then, the regulatory relationships among miRNA, TF, and genes were screened and the regulatory network was constructed. Finally, DAVID was used for KEGG enrichment analysis.ResultsThere were 11 upregulated IFG-related DMs and five upregulated T2DM-related DMs. Three of the DMs overlapped. In addition, there were eight downregulated IFG-related DMs and two downregulated T2DM-related DMs. Only one downregulated DM overlapped. Similarly, there were 264 upregulated IFG-related DGs and 331 upregulated T2DM-related DGs; and 196 overlapping genes were obtained. In addition, there were 400 downregulated IFG-related DMs and 568 downregulated T2DM-related DMs. A total of 326 downregulated DMs were overlapped. The overlapped DGs were enriched in various pathways, including hematopoietic cell lineage, Fc gamma R-mediated phagocytosis, and MAPK signaling pathway. TAF1 (upregulated gene) and MAFK (downregulated gene) were hub nodes both in IFG- and T2DM-related miRNA-TF-gene regulatory network. In addition, miRNAs, including hsa-miR-29a, hsa-miR-192, and hsa-miR-144, were upregulated hub nodes in the two regulatory networks.ConclusionsGenes including TAF1 and MAFK, and miRNAs including hsa-miR-29a, hsa-miR-192, and hsa-miR-144 might be potential target genes and important miRNAs for IFG and T2DM.

show abstract

Section: Discussionsupporting

confidence: 64%

Comparison of Transcriptome Between Type 2 Diabetes Mellitus and Impaired Fasting Glucose

Cui

Chi

et al. 2016

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…Ninety-five samples were excluded due to a low number of miRNAs expressed (≤200 miRNAs per sample), and in further analysis, 243 miRNAs that were expressed in at least 2/3 of the samples were included (number of miRNAs present in detectable levels in majority of the blood samples is well in line with previous similar analysis of blood tissue41). The RNA quality and functionality of the TaqMan OpenArray microRNA expression panels have been validated previously42. After quality control and removal of outlier miRNAs, profiling was successful on 871 samples.…”

Section: Methodsmentioning

confidence: 99%

Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism—The Young Finns Study

Raitoharju

Seppälä

Lyytikäinen

et al. 2016

Sci Rep

Self Cite

View full text Add to dashboard Cite

MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34–49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10−14 and FC = 1.25, p = 4.86 * 10−4, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10−8 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = −0.143, p = 1.00 * 10−4) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels.

show abstract

“…In another cohort, consisting of 68 type 1 diabetic patients treated with insulin for at least 6 months, urinary miR-126 was lower in type 1 diabetic patients compared with controls and was inversely correlated with HbA 1c levels [36]. In a third study, blood levels of miR-144-5p and miR-1207-5p reflected glucose and HbA 1c levels, respectively [48].…”

Section: Circulating Mirnas As Biomarkers Of Therapeutic Follow-upmentioning

confidence: 95%

“…Interestingly, in healthy male volunteers, the plasma level of these two miRNAs appears to be altered after insulin infusion followed by intralipid and heparin mixture infusion, which is known to induce insulin resistance [31]. A second study reported a correlation between levels of circulating miR-484 and metabolites related to insulin resistance, which points to the potential benefit of circulating miRNAs as biomarkers of insulin resistance [48].…”

Section: Circulating Mirnas As Biomarkers Of the Disease Processmentioning

confidence: 98%

Circulating microRNAs and diabetes: potential applications in medical practice

et al. 2015

View full text Add to dashboard Cite

The explosive increase in the worldwide prevalence of diabetes over recent years has transformed the disease into a major public health concern. While diabetes can be screened for and diagnosed by reliable biological tests based on blood glucose levels, by and large there are no means of detecting at-risk patients or of following diabetic complications. The recent discovery that microRNAs are not only chief intracellular players in many biological processes, including insulin secretion and action, but are also circulating, has put them in the limelight as possible biological markers. Here we discuss the potential role of circulating microRNAs as biomarkers in the context of diabetes and its associated complications.

show abstract

Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome

Cited by 69 publications

References 49 publications

Comparison of Transcriptome Between Type 2 Diabetes Mellitus and Impaired Fasting Glucose

Comparison of Transcriptome Between Type 2 Diabetes Mellitus and Impaired Fasting Glucose

Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism—The Young Finns Study

Circulating microRNAs and diabetes: potential applications in medical practice

Contact Info

Product

Resources

About