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LncRNA LYPLAL1, miR-204-5p, and SIRT1: novel signatures for risk assessment of diabetic macrovascular complications
Maysa A Mobasher1, Marwa A Shabana2, Mousa O Germoush3
1Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, 72388, Sakaka, Saudi Arabia. mmobasher@ju.edu.sa.
Insights
Diabetic microvascular complications (MVC) can be detected using lncRNA LYPLAL1, miR-204-5p, and SIRT1. LncRNA LYPLAL1 shows high sensitivity and specificity as an independent predictor of diabetic MVC.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Uncontrolled diabetes mellitus can cause micro- and macrovascular complications.
- Long non-coding RNA (lncRNA) LYPLAL1 plays a protective role by reducing endothelial inflammation.
- LYPLAL1 upregulates sirtuin 1 (SIRT1) and downregulates microRNA (miR)-204-5p.
Purpose of the Study:
- To investigate lncRNA LYPLAL1, miR-204-5p, and SIRT1 as diagnostic biomarkers for diabetic microvascular complications (MVC).
- To assess the clinical correlations of these molecules in patients with diabetes and MVC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) was used to measure lncRNA and miR expression levels.
- Enzyme-linked immunosorbent assay (ELISA) was employed to quantify SIRT1 levels.
- The study included 32 controls, 32 patients with diabetes alone, and 32 patients with diabetic MVC.
Main Results:
- lncRNA LYPLAL1 and SIRT1 levels were significantly lower in patients with MVC compared to those without.
- miR-204-5p levels were significantly higher in patients with MVC.
- lncRNA LYPLAL1 demonstrated high diagnostic performance (90.6% specificity, 96.9% sensitivity) and was an independent predictor of MVC.
Conclusions:
- The lncRNA LYPLAL1/miR-204-5p/SIRT1 axis serves as a potential diagnostic biomarker for diabetic MVC.
- A combination of these three markers achieved high accuracy (98.4%) in diagnosing diabetic MVC.
- LYPLAL1 expression is a significant independent predictor of MVC in diabetic patients.
Abstract:
Long-term, uncontrolled diabetes mellitus can lead to micro- and macrovascular problems. The protective function of lncRNA LYPLAL1 is to reduce endothelium cell inflammation by upregulating sirtuin 1 (SIRT1) and reducing microRNA (miR)-204-5p. This work attempted to examine the lncRNA LYPLAL1/miR-204-5p/SIRT1 molecules as diagnostic biomarkers for diabetic MVC and to assess their clinical correlations. The study enrolled 32 controls, 32 patients with diabetes alone, and 32 patients with diabetic MVC. RT-qPCR, or quantitative real-time PCR, was utilized to determine the expression levels of lncRNA and miR. SIRT1 was measured by ELISA. When comparing cases with MVC to those without MVC, the lncRNA LYPLAL1 and SIRT1 values were significantly lower. Conversely, patients with MVC had significantly higher miR-204-5p levels than those without MVC. The LncRNA LYPLAL1 performed best in terms of detecting MVC. It attained 90.6% specificity and 96.9% sensitivity. A combination of three markers (lncRNA LYPLAL1, miR-204-5p, and SIRT1) yielded the best accuracy at 98.4%. LYPLAL1 expression appeared to be an independent MVC predictor. Adjusted OR for LYPLAL1 expression was 405 (95% CI: 1.4-1200) (p = 0.039). When we compared cases with MVC to those without MVC, the lncRNA LYPLAL1 and SIRT1 values were significantly lower. Patients with MVC had significantly higher miR-204-5p levels than those without MVC. LYPLAL1 LncRNA demonstrated the best performance characteristics. LncRNA LYPLAL1 expression is an independent predictor of MVC.
