Abstract
Aim: 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.Methods: 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.Results: All miRNAs were significantly overexpressed in subjects with known diabetes when compared to normotolerant individuals, as well as known diabetics vs. screen-detected (p<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, p=0.023).Conclusion: 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.
Highlights
MicroRNAs are a family of short, noncoding RNA molecules, averaging 22 nucleotides in length, responsible for regulating gene expression by repressing the translation of messenger RNA molecules, as well as by destabilization of the mRNA molecules (Zhou et al, 2015; O’Brien et al, 2018)
All miRNAs were significantly overexpressed in subjects with known diabetes when compared to normotolerant individuals (p < 0.001), and a significant elevation was observed in known diabetics vs. screen-detected (p < 0.001; Figure 1). miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p were all significantly upregulated in screen-detected diabetes mellitus (DM) compared to the normotolerant group (p ≤ 0.013), with the exception of miR-30e-3p (p = 0.145), and miR-30a-5p exhibited the most significant increase in expression (p = 0.001) between the two groups
In light of the scarcity of reports pertaining to long-term T2DM and miR-182-5p expression, we have shown that the time span of disease in known diabetics has more of an influence on the expression of the miRNA, as opposed to treatment
Summary
MicroRNAs (miRNAs) are a family of short, noncoding RNA molecules, averaging 22 nucleotides in length, responsible for regulating gene expression by repressing the translation of messenger RNA (mRNA) molecules, as well as by destabilization of the mRNA molecules (Zhou et al, 2015; O’Brien et al, 2018) Since their discovery, miRNAs have been found to play key roles in the regulation of pathways associated with various diseases, including cancers (Liu et al, 2017; Zhang et al, 2019), cardiovascular diseases (Maciejak et al, 2018; Zhu et al, 2019), and diabetes mellitus (DM; Zampetaki et al, 2010; Massaro et al, 2019; Wang et al, 2019). The focus has progressively extended toward assessing miRNA expression levels and treatment of disease (Walayat et al, 2018)
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