Weale Cecil J, Matshazi Don M, Davids Saarah F G, Raghubeer Shanel, Erasmus Rajiv T, Kengne Andre P, Davison Glenda M, Matsha Tandi E
SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town, South Africa.
National Health Laboratory Service (NHLS), Division of Chemical Pathology, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa.
Front Genet. 2021 Sep 8;12:702410. doi: 10.3389/fgene.2021.702410. eCollection 2021.
The influence of disease duration and anti-diabetic treatment on epigenetic processes has been described, with limited focus on interactions with microRNAs (miRNAs). miRNAs have been found to play key roles in the regulation of pathways associated with type 2 diabetes mellitus (T2DM), and expression patterns in response to treatment may further promote their use as therapeutic targets in T2DM and its associated complications. We therefore aimed to investigate the expressions of circulating miRNAs (miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p) in newly diagnosed and known diabetics on treatment, in South Africa. A total of 1254 participants with an average age of 53.8years were included in the study and classified according to glycaemic status (974 normotolerant, 92 screen-detected diabetes and 188 known diabetes). Whole blood levels of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p were quantitated using RT-qPCR. Expression analysis was performed and compared across groups. All miRNAs were significantly overexpressed in subjects with known diabetes when compared to normotolerant individuals, as well as known diabetics vs. screen-detected (<0.001). Upon performing regression analysis, of all miRNAs, only miR-182-5p remained associated with the duration of the disease after adjustment for type of treatment (OR: 0.127, CI: 0.018-0.236, =0.023). Our findings revealed important associations and altered expression patterns of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p in known diabetics on anti-diabetic treatment compared to newly diagnosed individuals. Additionally, miR-182-5p expression decreased with increasing duration of T2DM. Further studies are, however, recommended to shed light on the involvement of the miRNA in insulin signalling and glucose homeostasis, to endorse its use as a therapeutic target in DM and its associated complications.
疾病持续时间和抗糖尿病治疗对表观遗传过程的影响已有描述,但对与微小RNA(miRNA)相互作用的关注有限。已发现miRNA在2型糖尿病(T2DM)相关通路的调节中起关键作用,其对治疗的反应性表达模式可能进一步促进其作为T2DM及其相关并发症治疗靶点的应用。因此,我们旨在研究南非新诊断和正在接受治疗的糖尿病患者中循环miRNA(miR-30a-5p、miR-1299、miR-182-5p、miR-30e-3p和miR-126-3p)的表达情况。共有1254名平均年龄为53.8岁的参与者纳入本研究,并根据血糖状态进行分类(974名糖耐量正常者、92名筛查发现的糖尿病患者和188名已知糖尿病患者)。采用逆转录定量聚合酶链反应(RT-qPCR)对miR-30a-5p、miR-1299、miR-182-5p、miR-30e-3p和miR-126-3p的全血水平进行定量。进行表达分析并在各亚组间进行比较。与糖耐量正常个体相比,所有miRNA在已知糖尿病患者中均显著过表达,已知糖尿病患者与筛查发现的糖尿病患者相比也显著过表达(<0.001)。进行回归分析后,在所有miRNA中,仅miR-182-5p在调整治疗类型后仍与疾病持续时间相关(比值比:0.127,可信区间:0.018-0.236,P=0.023)。我们的研究结果揭示了在接受抗糖尿病治疗的已知糖尿病患者中,与新诊断个体相比,miR-30a-5p、miR-1299、miR-182-5p、miR-30e-3p和miR-126-3p存在重要关联且表达模式改变。此外,miR-182-5p的表达随T2DM持续时间的增加而降低。然而,建议进一步研究以阐明miRNA在胰岛素信号传导和葡萄糖稳态中的作用,以支持其作为糖尿病及其相关并发症治疗靶点的应用。