Altered Expression of MiR-375 and MiR-541 in Type 2 Diabetes Patients with and Without Coronary Artery Disease (CAD): the Potential of MiR-375 As a CAD Biomarker

Overview

Journal J Diabetes Metab Disord

Specialty Endocrinology

Date 2024 Jun 27

PMID 38932834

Authors

Parisa Sangali

Sara Abdullahi

Mani Nosrati

Omeh Farveh Khosravi-Asrami

Abdolkarim Mahrooz

Abouzar Bagheri

Affiliations

Soon will be listed here.

Abstract

Background: MicroRNAs (miRNAs, miRs) have been linked to beta-cell pathologies and have also shown potential as biomarkers for cardiovascular disease. This study aimed to evaluate the expression of miR-375 and miR-541 in T2D patients with and without CAD, in order to determine the potential of these miRNAs as biomarkers for assessing CAD risk.

Methods: This study was conducted on 106 patients with T2D who underwent coronary angiographic examination. Reverse transcription was performed using the cDNA synthesis kit. Real-time PCR was performed using the SYBR Green method and specific primers. The ability to predict which person had developed CAD was evaluated by calculating the area under the receiver-operating characteristic (ROC) curve (AUC).

Results: The expression of miR-375 was significantly higher in samples from CAD patients compared to those without CAD ( = 0.009). While the expression of miR-541 was also higher in CAD patients, the difference was not statistically significant. In terms of predicting CAD, miR-375 was found to be a suitable predictor with an AUC of 0.74 ( = 0.01), while miR-541 was not. With a cut-off value of 0.016 for miR-375, the sensitivity was 67% and the specificity was 80%.

Conclusion: Our results indicated that circulating levels of miR-375 and miR-541 were elevated in T2D patients with CAD compared to those without CAD. This suggests that miR-375 could potentially be used as a non-invasive biomarker for the diagnosis of CAD in T2D patients.

Citing Articles

Novel Micro-Ribonucleic Acid Biomarkers for Early Detection of Type 2 Diabetes Mellitus and Associated Complications-A Literature Review.

Ahmed S, Adnan H, Khawaja M, Butler A Int J Mol Sci. 2025; 26(2).

PMID: 39859467 PMC: 11765584. DOI: 10.3390/ijms26020753.

Identification of plasma miR-4505, miR-4743-5p and miR-4750-3p as novel diagnostic biomarkers for coronary artery disease in patients with type 2 diabetes mellitus: a case-control study.

Szydelko J, Czop M, Petniak A, Lenart-Lipinska M, Kocki J, Zapolski T Cardiovasc Diabetol. 2024; 23(1):278.

PMID: 39080630 PMC: 11287982. DOI: 10.1186/s12933-024-02374-0.

References

Mahrooz A, Mackness M . Epigenetics of paraoxonases. Curr Opin Lipidol. 2020; 31(4):200-205. DOI: 10.1097/MOL.0000000000000687. View

Zhu H, Leung S . Identification of microRNA biomarkers in type 2 diabetes: a meta-analysis of controlled profiling studies. Diabetologia. 2015; 58(5):900-11. DOI: 10.1007/s00125-015-3510-2. View

Wang Y, Dong X, Li Z, Wang W, Tian J, Chen J . Downregulated RASD1 and upregulated miR-375 are involved in protective effects of calycosin on cerebral ischemia/reperfusion rats. J Neurol Sci. 2014; 339(1-2):144-8. DOI: 10.1016/j.jns.2014.02.002. View

Mahrooz A, Khosravi-Asrami O, Alizadeh A, Mohmmadi N, Bagheri A, Kashi Z . Can HDL cholesterol be replaced by paraoxonase 1 activity in the prediction of severe coronary artery disease in patients with type 2 diabetes?. Nutr Metab Cardiovasc Dis. 2023; 33(8):1599-1607. DOI: 10.1016/j.numecd.2023.05.020. View

Chang X, Li S, Li J, Yin L, Zhou T, Zhang C . Ethnic differences in microRNA-375 expression level and DNA methylation status in type 2 diabetes of Han and Kazak populations. J Diabetes Res. 2014; 2014:761938. PMC: 3972833. DOI: 10.1155/2014/761938. View

Tang X, Tang G, Ozcan S . Role of microRNAs in diabetes. Biochim Biophys Acta. 2008; 1779(11):697-701. PMC: 2643014. DOI: 10.1016/j.bbagrm.2008.06.010. View

Liu W, Zhao X, Zhang Y, Fang G, Xue Y . MicroRNA-375 as a potential serum biomarker for the diagnosis, prognosis, and chemosensitivity prediction of osteosarcoma. J Int Med Res. 2017; 46(3):975-983. PMC: 5972241. DOI: 10.1177/0300060517734114. View

Li X . MiR-375, a microRNA related to diabetes. Gene. 2013; 533(1):1-4. DOI: 10.1016/j.gene.2013.09.105. View

Wu X, Li Y, Man B, Li D . Assessing MicroRNA-375 Levels in Type 2 Diabetes Mellitus (T2DM) Patients and Their First-Degree Relatives with T2DM. Diabetes Metab Syndr Obes. 2021; 14:1445-1451. PMC: 8018570. DOI: 10.2147/DMSO.S298735. View

10.

Garcia-Jacobo R, Uresti-Rivera E, Portales-Perez D, Gonzalez-Amaro R, Lara-Ramirez E, Enciso-Moreno J . Circulating miR-146a, miR-34a and miR-375 in type 2 diabetes patients, pre-diabetic and normal-glycaemic individuals in relation to β-cell function, insulin resistance and metabolic parameters. Clin Exp Pharmacol Physiol. 2019; 46(12):1092-1100. DOI: 10.1111/1440-1681.13147. View

11.

Mahrooz A, Shokri Y, Variji A, Zargari M, Alizadeh A, Mehtarian E . Improved risk assessment of coronary artery disease by substituting paraoxonase 1 activity for HDL-C: Novel cardiometabolic biomarkers based on HDL functionality. Nutr Metab Cardiovasc Dis. 2021; 31(4):1166-1176. DOI: 10.1016/j.numecd.2020.12.026. View

12.

Kianmehr A, Qujeq D, Bagheri A, Mahrooz A . Oxidized LDL-regulated microRNAs for evaluating vascular endothelial function: molecular mechanisms and potential biomarker roles in atherosclerosis. Crit Rev Clin Lab Sci. 2021; 59(1):40-53. DOI: 10.1080/10408363.2021.1974334. View

13.

Liu F, Li N, Long B, Fan Y, Liu C, Zhou Q . Cardiac hypertrophy is negatively regulated by miR-541. Cell Death Dis. 2014; 5:e1171. PMC: 5424117. DOI: 10.1038/cddis.2014.141. View

14.

Mokhtari H, Yaghmaei B, Sirati-Sabet M, Jafari N, Mardomi A, Abediankenari S . Epigallocatechin-3-gallate Enhances the Efficacy of MicroRNA-34a Mimic and MicroRNA-93 Inhibitor Co-transfection in Prostate Cancer Cell Line. Iran J Allergy Asthma Immunol. 2021; 19(6):612-623. DOI: 10.18502/ijaai.v19i6.4930. View

15.

Ballian N, Brunicardi F . Islet vasculature as a regulator of endocrine pancreas function. World J Surg. 2007; 31(4):705-14. DOI: 10.1007/s00268-006-0719-8. View

16.

Mishan M, Tabari M, Parnian J, Fallahi J, Mahrooz A, Bagheri A . Functional mechanisms of miR-192 family in cancer. Genes Chromosomes Cancer. 2020; . DOI: 10.1002/gcc.22889. View

17.

Mahrooz A, Alizadeh A, Gohari G . The salt stimulation property of serum paraoxonase (PON1) could be a valuable factor in evaluating the enzyme status in ischemic stroke: the role of activity-determined PON1 192Q/R phenotypes. J Neurol Sci. 2014; 338(1-2):197-202. DOI: 10.1016/j.jns.2014.01.006. View

18.

Mahrooz A, Alizadeh A, Hashemi-Soteh M, Ghaffari-Cherati M, Hosseyni-Talei S . Polymorphic Variants rs3088442 and rs2292334 in the Organic Cation Transporter 3 (OCT3) Gene and Susceptibility Against Type 2 Diabetes: Role of their Interaction. Arch Med Res. 2017; 48(2):162-168. DOI: 10.1016/j.arcmed.2017.03.010. View

19.

LaPierre M, Stoffel M . MicroRNAs as stress regulators in pancreatic beta cells and diabetes. Mol Metab. 2017; 6(9):1010-1023. PMC: 5605735. DOI: 10.1016/j.molmet.2017.06.020. View

20.

Joglekar M, Joglekar V, Hardikar A . Expression of islet-specific microRNAs during human pancreatic development. Gene Expr Patterns. 2008; 9(2):109-13. DOI: 10.1016/j.gep.2008.10.001. View