Serum levels miR-391-3p and miR-221-3p as potential biomarkers for diagnosis of diabetes
Abstract
Objectives: Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance and progressive β-cell dysfunction. Early detection is extremely important for effective management and the prevention of complications. Circulating microRNAs (miRNAs) been found to be promising non-invasive biomarkers for a variety of diseases, including metabolic disorders. The purpose of this study was to assess the diagnostic potential of serum microRNA-29a-3p (miR-29a-3p) and microRNA-221-3p (miR-221-3p) in patients with T2D.
Methods: A case-control study was conducted involving 48 T2D patients and 42 healthy controls. Serum levels of miR-29a-3p and miR-221-3p were quantified using real-time PCR.
Results: Both miR-29a-3p and miR-221-3p were significantly increased in sera of T2D patients compared to controls. Serum miR-29a-3p and miR-221-3p were positively correlated with fasting blood glucose (r = 0.466), (r = 0.403) and HbA1c (r = 0.375), (r = 0.366), respectively. miR-29a-3p showed moderate correlations with TG (r = 0.300) after adjustment for BMI, age and gender. Both miRNAs also correlated with adiposity parameters such as body mass index, weight and waist circumference.
Conclusion: Serum miR-29a-3p and miR-221-3p are significantly upregulated in T2D and correlate with key metabolic markers. Their diagnostic performance suggests that they can function as valuable non-invasive biomarkers for the early detection and monitoring of T2D. Further research is needed to examine these results in larger and more diverse population groups.
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8. Gentile AM, Lhamyani S, Mengual-Mesa M, García-Fuentes E, Bermúdez-Silva FJ, Rojo-Martínez G, et al. MiR-221-3p/222-3p Cluster Expression in Human Adipose Tissue Is Related to Obesity and Type 2 Diabetes. Int J Mol Sci. 2023;24(24).
9. Zhao L, Pan Q. Highly-Expressed MiR-221-3p Distinctly Increases the Incidence of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus. Transl Vis Sci Technol. 2023;12(10):17.
10. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S20-s42.
11. Udesen PB, Glintborg D, Sørensen AE, Svendsen R, Nielsen NLS, Wissing MLM, et al. Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome. Endocrine connections. 2020;9(11):1075-84.
12. Jimenez-Lucena R, Alcala-Diaz JF, Roncero-Ramos I, Lopez-Moreno J, Camargo A, Gomez-Delgado F, et al. MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study. Clinical Nutrition. 2021;40(3):1028-38.
13. Pandey AK, Verma G, Vig S, Srivastava S, Srivastava AK, Datta M. miR-29a levels are elevated in the db/db mice liver and its overexpression leads to attenuation of insulin action on PEPCK gene expression in HepG2 cells. Molecular and cellular endocrinology. 2011;332(1-2):125-33.
14. Liang J, Liu C, Qiao A, Cui Y, Zhang H, Cui A, et al. MicroRNA-29a-c decrease fasting blood glucose levels by negatively regulating hepatic gluconeogenesis. Journal of hepatology. 2013;58(3):535-42.
15. Hung Y-H, Kanke M, Kurtz CL, Cubitt R, Bunaciu RP, Miao J, et al. Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice. Physiological Genomics. 2019;51(8):379-89.
16. Kurtz CL, Peck BC, Fannin EE, Beysen C, Miao J, Landstreet SR, et al. MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism genes and is dysregulated in animal models of insulin resistance and diabetes. Diabetes. 2014;63(9):3141-8.
17. Dooley J, Garcia-Perez JE, Sreenivasan J, Schlenner SM, Vangoitsenhoven R, Papadopoulou AS, et al. The microRNA-29 family dictates the balance between homeostatic and pathological glucose handling in diabetes and obesity. Diabetes. 2016;65(1):53-61.
18. Massart J, Sjögren RJ, Lundell LS, Mudry JM, Franck N, O’Gorman DJ, et al. Altered miR-29 expression in type 2 diabetes influences glucose and lipid metabolism in skeletal muscle. Diabetes. 2017;66(7):1807-18.
19. Yang W-M, Jeong H-J, Park S-Y, Lee W. Induction of miR-29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS-1 in myocytes. FEBS letters. 2014;588(13):2170-6.
20. He A, Zhu L, Gupta N, Chang Y, Fang F. Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Molecular endocrinology. 2007;21(11):2785-94.
21. Glantschnig C, Koenen M, Gil‐Lozano M, Karbiener M, Pickrahn I, Williams‐Dautovich J, et al. A miR‐29a‐driven negative feedback loop regulates peripheral glucocorticoid receptor signaling. The FASEB Journal. 2019;33(5):5924-41.
22. Mysore R, Ortega FJ, Latorre J, Ahonen M, Savolainen-Peltonen H, Fischer-Posovszky P, et al. MicroRNA-221-3p regulates angiopoietin-like 8 (ANGPTL8) expression in adipocytes. The Journal of Clinical Endocrinology & Metabolism. 2017;102(11):4001-12.
23. Peng J, Zhou Y, Deng Z, Zhang H, Wu Y, Song T, et al. miR‐221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin‐1 (SIRT1). Journal of cellular biochemistry. 2018;119(8):6418-28.
24. Meerson A, Traurig M, Ossowski V, Fleming J, Mullins M, Baier L. Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-α. Diabetologia. 2013;56:1971-9.
25. Ahonen MA, Asghar MY, Parviainen SJ, Liebisch G, Höring M, Leidenius M, et al. Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2021;1866(1):158841.
26. Chan GCK, Than WH, Kwan BCH, Lai KB, Chan RCK, Teoh JYC, et al. Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis. Nutrients. 2022;14(22).
27. Abdel-Tawab MS, Mohamed MG, Doudar NA, Rateb EE, Reyad HR, Elazeem NAA. Circulating hsa-miR-221 as a possible diagnostic and prognostic biomarker of diabetic nephropathy. Mol Biol Rep. 2023;50(12):9793-803.
28. Lightell DJ, Jr., Moss SC, Woods TC. Upregulation of miR-221 and -222 in response to increased extracellular signal-regulated kinases 1/2 activity exacerbates neointimal hyperplasia in diabetes mellitus. Atherosclerosis. 2018;269:71-8.
2. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843.
3. Ghorbani S, Mahdavi R, Alipoor B, Panahi G, Nasli Esfahani E, Razi F, et al. Decreased serum microRNA-21 level is associated with obesity in healthy and type 2 diabetic subjects. Archives of physiology and biochemistry. 2018;124(4):300-5.
4. Mahdavi R, Ghorbani S, Alipoor B, Panahi G, Khodabandehloo H, Esfahani EN, et al. Decreased serum level of miR-155 is associated with obesity and its related metabolic traits. Clinical Laboratory. 2018;64.
5. Kraczkowska W, Stachowiak L, Pławski A, Jagodziński PP. Circulating miRNA as potential biomarkers for diabetes mellitus type 2: should we focus on searching for sex differences? J Appl Genet. 2022;63(2):293-303.
6. Dalgaard LT, Sørensen AE, Hardikar AA, Joglekar MV. The microRNA-29 family: role in metabolism and metabolic disease. Am J Physiol Cell Physiol. 2022;323(2):C367-c77.
7. Villard A, Marchand L, Thivolet C, Rome S. Diagnostic value of cell-free circulating microRNAs for obesity and type 2 diabetes: a meta-analysis. Journal of molecular biomarkers & diagnosis. 2015;6(6):251.
8. Gentile AM, Lhamyani S, Mengual-Mesa M, García-Fuentes E, Bermúdez-Silva FJ, Rojo-Martínez G, et al. MiR-221-3p/222-3p Cluster Expression in Human Adipose Tissue Is Related to Obesity and Type 2 Diabetes. Int J Mol Sci. 2023;24(24).
9. Zhao L, Pan Q. Highly-Expressed MiR-221-3p Distinctly Increases the Incidence of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus. Transl Vis Sci Technol. 2023;12(10):17.
10. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S20-s42.
11. Udesen PB, Glintborg D, Sørensen AE, Svendsen R, Nielsen NLS, Wissing MLM, et al. Metformin decreases miR-122, miR-223 and miR-29a in women with polycystic ovary syndrome. Endocrine connections. 2020;9(11):1075-84.
12. Jimenez-Lucena R, Alcala-Diaz JF, Roncero-Ramos I, Lopez-Moreno J, Camargo A, Gomez-Delgado F, et al. MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study. Clinical Nutrition. 2021;40(3):1028-38.
13. Pandey AK, Verma G, Vig S, Srivastava S, Srivastava AK, Datta M. miR-29a levels are elevated in the db/db mice liver and its overexpression leads to attenuation of insulin action on PEPCK gene expression in HepG2 cells. Molecular and cellular endocrinology. 2011;332(1-2):125-33.
14. Liang J, Liu C, Qiao A, Cui Y, Zhang H, Cui A, et al. MicroRNA-29a-c decrease fasting blood glucose levels by negatively regulating hepatic gluconeogenesis. Journal of hepatology. 2013;58(3):535-42.
15. Hung Y-H, Kanke M, Kurtz CL, Cubitt R, Bunaciu RP, Miao J, et al. Acute suppression of insulin resistance-associated hepatic miR-29 in vivo improves glycemic control in adult mice. Physiological Genomics. 2019;51(8):379-89.
16. Kurtz CL, Peck BC, Fannin EE, Beysen C, Miao J, Landstreet SR, et al. MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism genes and is dysregulated in animal models of insulin resistance and diabetes. Diabetes. 2014;63(9):3141-8.
17. Dooley J, Garcia-Perez JE, Sreenivasan J, Schlenner SM, Vangoitsenhoven R, Papadopoulou AS, et al. The microRNA-29 family dictates the balance between homeostatic and pathological glucose handling in diabetes and obesity. Diabetes. 2016;65(1):53-61.
18. Massart J, Sjögren RJ, Lundell LS, Mudry JM, Franck N, O’Gorman DJ, et al. Altered miR-29 expression in type 2 diabetes influences glucose and lipid metabolism in skeletal muscle. Diabetes. 2017;66(7):1807-18.
19. Yang W-M, Jeong H-J, Park S-Y, Lee W. Induction of miR-29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS-1 in myocytes. FEBS letters. 2014;588(13):2170-6.
20. He A, Zhu L, Gupta N, Chang Y, Fang F. Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Molecular endocrinology. 2007;21(11):2785-94.
21. Glantschnig C, Koenen M, Gil‐Lozano M, Karbiener M, Pickrahn I, Williams‐Dautovich J, et al. A miR‐29a‐driven negative feedback loop regulates peripheral glucocorticoid receptor signaling. The FASEB Journal. 2019;33(5):5924-41.
22. Mysore R, Ortega FJ, Latorre J, Ahonen M, Savolainen-Peltonen H, Fischer-Posovszky P, et al. MicroRNA-221-3p regulates angiopoietin-like 8 (ANGPTL8) expression in adipocytes. The Journal of Clinical Endocrinology & Metabolism. 2017;102(11):4001-12.
23. Peng J, Zhou Y, Deng Z, Zhang H, Wu Y, Song T, et al. miR‐221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin‐1 (SIRT1). Journal of cellular biochemistry. 2018;119(8):6418-28.
24. Meerson A, Traurig M, Ossowski V, Fleming J, Mullins M, Baier L. Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism downstream of leptin and TNF-α. Diabetologia. 2013;56:1971-9.
25. Ahonen MA, Asghar MY, Parviainen SJ, Liebisch G, Höring M, Leidenius M, et al. Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2021;1866(1):158841.
26. Chan GCK, Than WH, Kwan BCH, Lai KB, Chan RCK, Teoh JYC, et al. Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis. Nutrients. 2022;14(22).
27. Abdel-Tawab MS, Mohamed MG, Doudar NA, Rateb EE, Reyad HR, Elazeem NAA. Circulating hsa-miR-221 as a possible diagnostic and prognostic biomarker of diabetic nephropathy. Mol Biol Rep. 2023;50(12):9793-803.
28. Lightell DJ, Jr., Moss SC, Woods TC. Upregulation of miR-221 and -222 in response to increased extracellular signal-regulated kinases 1/2 activity exacerbates neointimal hyperplasia in diabetes mellitus. Atherosclerosis. 2018;269:71-8.
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| Issue | Vol 2 No 3 (2024) | |
| Section | Original Articles | |
| Keywords | ||
| miR-29a-3p miR-221-3p Serum Diabetes Circulation | ||
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How to Cite
1.
Mahdavi R, Jahangard R, Nasli Esfahani E, Razi F, Meshkani R. Serum levels miR-391-3p and miR-221-3p as potential biomarkers for diagnosis of diabetes. ABI. 2024;2(3):155-161.
