Serum microRNA profiling and bioinformatics analysis of patients with type 2 diabetes mellitus in a Chinese population

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by islet β-cell dysfunction and insulin resistance, which leads to an inability to maintain blood glucose homeostasis. Circulating microRNAs (miRNAs) have been suggested as novel biomarkers for T2DM prediction or disease progression. However, miRNAs and their roles in the pathogenesis of T2DM remain to be fully elucidated. In the present study, the serum miRNA expression profiles of T2DM patients in Chinese cohorts were examined. Total RNA was extracted from serum samples of 10 patients with T2DM and five healthy controls, and these was used in reverse-transcription-quantitative polymerase chain reaction analysis with the Exiqon PCR system of 384 serum/plasma miRNAs. A total of seven miRNAs were differentially expressed between the two groups (fold change >3 or <0.33; P<0.05). The serum expression levels of miR-455-5p, miR-454-3p, miR-144-3p and miR-96-5p were higher in patients with T2DM, compared with those of healthy subjects, however, the levels of miR-409-3p, miR-665 and miR-766-3p were lower. Hierarchical cluster analysis indicated that it was possible to separate patients with T2DM and control individuals into their own similar categories by these differential miRNAs. Target prediction showed that 97 T2DM candidate genes were potentially modulated by these seven miRNAs. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 24 pathways were enriched for these genes, and the majority of these pathways were enriched for the targets of induced and repressed miRNAs, among which insulin, adipocytokine and T2DM pathways, and several cancer-associated pathways have been previously associated with T2DM. In conclusion, the present study demonstrated that serum miRNAs may be novel biomarkers for T2DM and provided novel insights into the pathogenesis of T2DM.

Circular RNA hsa_circ_0056836 functions an oncogenic gene in hepatocellular carcinoma through modulating miR-766-3p/FOSL2 axis

“…Aberrant miR-766-3p expressions in renal cell carcinoma and HCC have been reported [13,14]. MiR-766-3p reveals as an inhibitor or inducer of tumor progression in various cancer types and it has recently received much attention since its significant role in human cancer [15,16]. However, it's interesting to note that miR-766-3p expression is reduced in HCC compared with noncancerous liver tissues, demonstrating that miR-766-3p may be a potential tumor suppressor in HCC [15].…”

MicroRNA-96 Promotes Vascular Repair in Oxygen-Induced Retinopathy—A Novel Uncovered Vasoprotective Function

“…N = 6-8 retinas/group. streptozotocin-induced diabetes rats (Wu et al, 2012) and in the plasma of type-2 diabetic patients (Yang et al, 2017), while miR-96 is downregulated in the RHO-mouse retina, a model for common form of inherited blindness (Palfi et al, 2016). In addition, hypoxic conditions in cancer cells have shown to modify the expression profiling of miRNAs (Shen et al, 2013;Bandara et al, 2017).…”

Exercise Training-Induced Changes in MicroRNAs: Beneficial Regulatory Effects in Hypertension, Type 2 Diabetes, and Obesity

“…IRS-1 levels also showed a negative correlation with increased miR-144 expression in the whole blood of T2D subjects, exhibiting a correlation with progressively increased glycemic status [ 127 ]. In another study, miR-96-5p, which also targets IRS-1, was found overexpressed in the serum of T2D subjects, along with miR-144-3p, miR-454-3p, and miR-455-5p, while miR-409-3p, miR-665, and miR-766-3p were reduced [ 128 ]. IRS-1 is also negatively regulated by miR-126, which was found to be overexpressed by hepatocytes in an in vitro model of insulin resistance [ 129 ].…”

“…MiR-144 is overexpressed in T2D and regulates the IRS, the initiator of insulin signaling [ 127 , 128 ]. This is one of the molecular mechanisms leading to insulin resistance.…”