Long non-coding RNAs in metabolic disorders: pathogenetic relevance and potential biomarkers and therapeutic targets.

BACKGROUND: It has been suggested that dysregulation of long non-coding RNAs (lncRNAs) could be associated with the incidence and development of metabolic disorders. AIM: Accordingly, this narrative review described the molecular mechanisms of lncRNAs in the development of metabolic diseases including insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), cirrhosis, and coronary artery diseases (CAD). Furthermore, we investigated the up-to-date findings on the association of deregulated lncRNAs in the metabolic disorders, and potential use of lncRNAs as biomarkers and therapeutic targets. CONCLUSION: LncRNAs/miRNA/regulatory proteins axis plays a crucial role in progression of metabolic disorders and may be used in development of therapeutic and diagnostic approaches.

The rs2910164 variant is associated with reduced miR-146a expression but not cytokine levels in patients with type 2 diabetes.

PURPOSE: Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels. METHODS: The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164. The RNA expression levels were determined by real-time PCR. Moreover, TNF-α, IL-6, IL-10 and IL-1ß serum levels were measured using ELISA method. RESULTS: Our results showed that the miR-146a expression levels were significantly decreased in PBMCs (P = 0.004) and plasma (P = 0.008) samples of patients with T2D compared to healthy participants. In addition, we observed that IRAK1 mRNA expression-but not TLR4, TRAF6 and NFĸB-was significantly increased in patients with T2D compared to controls (P = 0.028). The relative expression levels of miR-146a in plasma and PBMCs samples of diabetic patients with the rs2910164 GG genotypes were significantly higher than that in CC (P < 0.05). Moreover, no significant differences were found in miR-146a targets and cytokine levels between the rs2910164 different genotypes. CONCLUSION: Our study demonstrated that miR-146a circulating levels were significantly elevated in controls compared with T2D patients. In addition, we identified that rs2910164-C allele is associated with reduced expression levels of the miR-146a but not its mRNAs targets and cytokine levels in diabetic patients.

THE ASSOCIATION OF PLASMA LEVELS OF miR-34a AND miR-149 WITH OBESITY AND INSULIN RESISTANCE IN OBESE CHILDREN AND ADOLESCENTS.

CONTEXT: MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. OBJECTIVE: The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. DESIGN: Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by ΔCt method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). RESULTS: miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. CONCLUSIONS: miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR-149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA.

The pre-mir-27a variant rs895819 may contribute to type 2 diabetes mellitus susceptibility in an Iranian cohort.

PURPOSE: The study was aimed at investigating the association between hsa-mir-27a polymorphism rs895819 (T/C) and type 2 diabetes mellitus (T2DM) susceptibility in a large Iranian cohort. METHODS: In this case-control study, the investigated population consisted of T2DM patients (n = 204) and sex- and age-matched controls (n = 209). We used the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for genotyping. RESULTS: We observed significant differences between T2DM patients and controls for weight (p = 0.002), BMI (p < 0.001), systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.001), triglyceride (p = 0.004) and LDL cholesterol (p = 0.051). Moreover, we found that genotype distributions were significantly different between groups (p < 0.05) and that the rs895819-C allele is more frequent in controls (p = 0.030, OR = 0.72, 95 % CI 0.53-0.97). CONCLUSION: Our study shows that rs895819 in hsa-mir-27a is associated with T2DM susceptibility and that the C allele conveyed a protective role against T2DM. Larger multicentric and specific functional studies will be necessary to obtain a deeper comprehension of the role of rs895819 and hsa-mir-27a and how they are involved in the development of diabetes.