Analysis of mRNA-miRNA-lncRNA differential expression in prediabetes/type 2 diabetes mellitus patients as potential players in insulin resistance

Abstract

IntroductionType 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients’ serum samples.MethodsWe used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR.ResultsThe levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups.DiscussionThe presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages.

Rosavin improves insulin resistance and alleviates hepatic and kidney damage via modulating the cGAS-STING pathway and autophagy signaling in HFD/STZ-induced T2DM animals

“…43 As a result, it is imperative to investigate the mechanism and pinpoint molecular targets for prompt diagnosis and treatment. 44 The pathogenesis of T2DM is very complex and involves inflammatory and immune reactions, epigenetic modulations, and signaling pathways. 43 Additionally, medication noncompliance due to side effects is a major limitation in T2DM treatment.…”

Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

“…miRNAs can influence insulin signaling by affecting the expression of INSR and IRS-1, the translocation of GLUT4, and the activity of PI3K; furthermore, they influence insulin secretion by regulating β-cell metabolic stress, proliferation, and survival, as well as regulating GSIS and improving insulin sensitivity [148][149][150][151]. Therefore, miR-NAs are potential biomarkers for diabetes prediction [152]. A meta-analysis revealed that miR-29a-3p, miR-221-3p, miR-126-3p, miR-26a-5p, miR-503-5p, miR-100-5p, miR-101-3p, mIR-103a-3p, miR-122-5p, miR-199a-3p, miR-30b-5p, miR-130a-3p, miR-143-3p, miR-145-5p, miR-19a-3p, and miR-311-3p (in order of importance) fulfill the criteria for biomarker selection [153].…”

Modulation of MicroRNAs and Exosomal MicroRNAs after Dietary Interventions for Obesity and Insulin Resistance: A Narrative Review

“…Ali and collaborators studied the serum levels of miRNAs, mRNAs, and lncRNAs (long noncoding RNAs) in subjects with type-2 diabetes, subjects with prediabetes, and healthy control subjects, with the purpose of identifying genes broadly related to the pathogenesis of insulin resistance and prediabetes. The results showed that the expression levels of TMEM173 (Transmembrane Protein 173), CHUK (Conserved Helix-loop-helix Ubiquitous Kinase), and the miRNAs miR-611, miR-5192, and miR-1976 gradually increased from the control group to the prediabetes group and reached their highest levels in the type-2 diabetes group, while the expression of lncRNAs RP4-60503.4 and AC074117.2 gradually decreased from the control group to the prediabetes group and reached their lowest levels in the type-2 diabetes group [55].…”