Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a multifactorial disorder that leads to alterations in gene regulation. Long non-coding RNAs (lncRNAs) have become a major research topic as they are involved in metabolic disorders.

Methods: This study included a total of 400 study subjects; 200 were subjects with T2DM and 200 were healthy subjects. Extracted RNA was used to synthesize cDNA by quantitative real time. Serum analysis was carried out to determine differences in biochemical parameters. Recorded data were used to evaluate associations with expression of lncRNAs NF-kappaB interacting lncRNA (NKILA), nuclear enriched abundant transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and myocardial infarction-associated transcript (MIAT) in T2DM cases.

Results: Compared with healthy controls, patients with T2DM showed an overall increase in expression of lncRNAs NKILA, NEAT, MALAT1, and MIAT by 3.94-fold, 5.28-fold, 4.46-fold, and 6.35-fold, respectively. Among patients with T2DM, higher expression of lncRNA NKILA was associated with hypertension (p=0.001), smoking (p<0.0001), and alcoholism (p<0.0001). Altered NEAT1 expression was significantly associated with weight loss (p=0.04), fatigue (p=0.01), slow wound healing (p=0.002), blurred vision (p=0.008), loss of appetite (p=0.007), smoking (p<0.0001), and alcoholism (p<0.0001). Higher expression of lncRNA MALAT1 was significantly linked with weight loss (p=0.003), blurred vision (p=0.01), smoking (p<0.0001), and alcoholism (p<0.0001). Expression of lncRNA MIAT was associated with only blurred vision (p<0.0001), smoking (p<0.0001), and alcoholism (p<0.0001). Positive correlations of lncRNA NKILA with lncRNAs NEAT1 (r=0.42, p<0.0001), MALAT (r=0.36, p<0.0001) and MIAT (r=0.42, p<0.0001) were observed among patients with T2DM. Significant positive correlations of lncRNA NEAT with lncRNAs MALAT and MIAT were observed among patients with T2DM. A positive correlation between lncRNAs MALAT and MIAT was also observed among patients with T2DM.

Conclusion: Increased circulating NKILA, NEAT1, MALAT, and MIAT expression in patients with T2DM, which is linked with poor patient outcomes and significantly linked with alcoholism and smoking, may influence the degree and severity of disease among patients with T2DM. These lncRNAs may contribute to the progression of T2DM disease or other related diabetes-related complications.

Keywords: RNA; blood pressure; diabetes mellitus; gene expression; type 2.

Figure 1

Correlation of expression of the lncRNA NKILA with that of the lncRNAs NEAT1, MALAT1, and MIAT among patients with type 1 diabetes mellitus. lncRNA, long non-coding RNA; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MIAT, myocardial infarction-associated transcript; NEAT1, nuclear enriched abundant transcript 1; NKILA, NF-kappaB interacting lncRNA.

Figure 2

Correlation of expression of the lncRNA NEAT with that of the lncRNAs MALAT1 and MIAT among patients with type 1 diabetes mellitus. lncRNA, long non-coding RNA; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MIAT, myocardial infarction-associated transcript; NEAT, nuclear enriched abundant transcript.

Figure 3

Correlation of expression of the lncRNAs MALAT1 and MIAT among patients with type 2 diabetes mellitus. lncRNA, long non-coding RNA; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MIAT, myocardial infarction-associated transcript.

Figure 4

ROC curve for lncRNA NKILA, NEAT1, MALAT1, and MIAT (A) with respect to patients with T2DM with nephropathy versus without nephropathy (B) with respect to patients with T2DM with retinopathy versus without retinopathy. lncRNA, long non-coding RNA; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MIAT, myocardial infarction-associated transcript; NEAT1, nuclear enriched abundant transcript 1; NKILA, NF-kappaB interacting lncRNA; ROC, receiver operating characteristic; T2DM, type 2 diabetes mellitus.