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Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study

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Abstract

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR < 30 mg/g, n = 136, NA), microalbuminuria (UACR at 30–300 mg/g, n = 132, MA), and clinical albuminuria (UACR > 300 mg/g, n = 122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects (P < 0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR (P < 0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

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References

  1. Sandeep V. Type 2 diabetes. Ann Intern Med 2015; 162(5): 231–242

    Google Scholar 

  2. Quiroga B, Arroyo D, de Arriba G. Present and future in the treatment of diabetic kidney disease. J Diabetes Res 2015; 2015: 801348

    PubMed  PubMed Central  Google Scholar 

  3. Toth-Manikowski S, Atta MG. Diabetic kidney disease: pathophysiology and therapeutic targets. J Diabetes Res 2015; 2015: 697010

    PubMed  PubMed Central  Google Scholar 

  4. Chamberlain JJ, Herman WH, Leal S, Rhinehart AS, Shubrook JH, Skolnik N, Kalyani RR. Pharmacologic therapy for type 2 diabetes: synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 2017; 166(8): 572–578

    PubMed  Google Scholar 

  5. Brownlee M, Aiello LP, Cooper ME, Vinik AI, Plutzky J, Boulton AJM. Chapter 33—Complications of Diabetes Mellitus. Elsevier Inc., 2016

  6. Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, Pasquinelli AE. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 2005; 122(4): 553–563

    CAS  PubMed  Google Scholar 

  7. Saito D, Maeshima Y, Nasu T, Yamasaki H, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Amelioration of renal alterations in obese type 2 diabetic mice by vasohibin-1, a negative feedback regulator of angiogenesis. Am J Physiol Renal Physiol 2011; 300(4): F873–F886

    CAS  PubMed  Google Scholar 

  8. Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, McMillan M, Kahn M, Kaminski N. Profibrotic role of miR-154 in pulmonary fibrosis. Am J Respir Cell Mol Biol 2012; 47(6): 879–887

    CAS  PubMed  PubMed Central  Google Scholar 

  9. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 2014; 37(Suppl 1): S14–S80

    Google Scholar 

  10. Chalmers J. The 1999 WHO-ISH Guidelines for the Management of Hypertension. Med J Aust 1999; 171(9): 458–459

    CAS  PubMed  Google Scholar 

  11. Affara M, Sanders D, Araki H, Tamada Y, Dunmore BJ, Humphreys S, Imoto S, Savoie C, Miyano S, Kuhara S, Jeffries D, Print C, Charnock-Jones DS. Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis. BMC Genomics 2013; 14(1): 23

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289(19): 2560–2572

    CAS  PubMed  Google Scholar 

  13. Yu R, Yang Y, Tian Y, Zhang Y, Lyu G, Zhu J, **ao L, Zhu J. The mechanism played by 1,25-dihydroxyvitamin D3 in treating renal fibrosis in diabetic nephropathy. Chin J Endocrinol Metab (Zhonghua Nei Fen Mi Dai **e Za Zhi) 2015; 9: 793–799 (in Chinese)

    Google Scholar 

  14. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3: 1–150

    Google Scholar 

  15. Wang YC, Li Y, Wang XY, Zhang D, Zhang H, Wu Q, He YQ, Wang JY, Zhang L, **a H, Yan J, Li X, Ying H. Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity. Diabetologia 2013; 56(10): 2275–2285

    CAS  PubMed  Google Scholar 

  16. Ng EK, Chong WW, ** H, Lam EK, Shin VY, Yu J, Poon TC, Ng SS, Sung JJ. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009; 58(10): 1375–1381

    CAS  PubMed  Google Scholar 

  17. Ortega FJ, Mercader JM, Moreno-Navarrete JM, Rovira O, Guerra E, Esteve E, **fra G, Martínez C, Ricart W, Rieusset J, Rome S, Karczewska-Kupczewska M, Straczkowski M, Fernández-Real JM. Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care 2014; 37(5): 1375–1383

    CAS  PubMed  Google Scholar 

  18. Shao Y, Ren H, Lv C, Ma X, Wu C, Wang Q. Changes of serum miR-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease. Endocrine 2017; 55(1): 130–138

    CAS  PubMed  Google Scholar 

  19. Ma X, Lu C, Lv C, Wu C, Wang Q. The expression of miR-192 and its significance in diabetic nephropathy patients with different urine albumin creatinine ratio. J Diabetes Res 2016; 2016: 6789402

    PubMed  PubMed Central  Google Scholar 

  20. Lv C, Zhou YH, Wu C, Shao Y, Lu CL, Wang QY. The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy. Diabetes Metab Res Rev 2015; 31 (7): 717–724

    CAS  PubMed  Google Scholar 

  21. Lin X, Yang Z, Zhang P, Liu Y, Shao G. miR-154 inhibits migration and invasion of human non-small cell lung cancer by targeting ZEB2. Oncol Lett 2016; 12(1): 301–306

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Dambal S, Giangreco AA, Acosta AM, Fairchild A, Richards Z, Deaton R, Wagner D, Vieth R, Gann PH, Kajdacsy-Balla A, Van der Kwast T, Nonn L. MicroRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma. J Steroid Biochem Mol Biol 2017; 167: 192–202

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Luk JM, Burchard J, Zhang C, Liu AM, Wong KF, Shek FH, Lee NP, Fan ST, Poon RT, Ivanovska I, Philippar U, Cleary MA, Buser CA, Shaw PM, Lee CN, Tenen DG, Dai H, Mao M. DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival. J Biol Chem 2011; 286(35): 30706–30713

    CAS  PubMed  PubMed Central  Google Scholar 

  24. **n C, Zhang H, Liu Z. miR-154 suppresses colorectal cancer cell growth and motility by targeting TLR2. Mol Cell Biochem 2014; 387(1–2): 271–277

    CAS  PubMed  Google Scholar 

  25. Gardiner E, Beveridge NJ, Wu JQ, Carr V, Scott RJ, Tooney PA, Cairns MJ. Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells. Mol Psychiatry 2012; 17(8): 827–840

    CAS  PubMed  Google Scholar 

  26. Formosa A, Markert EK, Lena AM, Italiano D, Finazzi-Agro’ E, Levine AJ, Bernardini S, Garabadgiu AV, Melino G, Candi E. MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene 2014; 33(44): 5173–5182

    CAS  PubMed  Google Scholar 

  27. Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaillé J. A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 2004; 14(9): 1741–1748

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Dixon-McIver A, East P, Mein CA, Cazier JB, Molloy G, Chaplin T, Andrew Lister T, Young BD, Debernardi S. Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS One 2008; 3(5): e2141

    PubMed  PubMed Central  Google Scholar 

  29. Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A, Brownstein MJ, Tuschl T, Margalit H. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 2005; 33(8): 2697–2706

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kaminski N, Benos P, Corcoran D, Pandit KV, Milosevic J, Yousef H. MicroRNAs In Idiopathic Pulmonary Fibrosis. Mosby, Inc., 2012. 191–199

  31. Yang H, Wang L, Zhao J, Chen Y, Lei Z, Liu X, **a W, Guo L, Zhang HT. TGF-β-activated SMAD3/4 complex transcriptionally upregulates N-cadherin expression in non-small cell lung cancer. Lung Cancer 2015; 87(3): 249–257

    PubMed  Google Scholar 

  32. Li Y, Hu F, Xue M, Jia YJ, Zheng ZJ, Wang L, Guan MP, Xue YM. Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in high glucose treated human mesangial cells. Biochem Biophys Res Commun 2017; 487(2): 216–222

    CAS  PubMed  Google Scholar 

  33. Huang J, Wu J, Li Y, Li X, Yang T, Yang Q, Jiang Y. Deregulation of serum microRNA expression is associated with cigarette smoking and lung cancer. BioMed Res Int 2014; 2014: 364316

    PubMed  PubMed Central  Google Scholar 

  34. Zheng Y, Zhu C, Ma L, Shao P, Qin C, Li P, Cao Q, Ju X, Cheng G, Zhu Q, Gu X, Hua L. miRNA-154-5p inhibits proliferation, migration and invasion by targeting E2F5 in prostate cancer cell lines. Urol Int 2017; 98(1): 102–110

    CAS  PubMed  Google Scholar 

  35. Ding J, Li JL, Yu MK. Expression of miRNA-154 in astrocytomas and its clinical significance. Chin Clin Oncol (Lin Chuang Zhong Liu Xue Za Zhi) 2017; 22(4): 314–318 (in Chinese)

    Google Scholar 

  36. Liu HY, Zhang CH. China’s urban and rural public health resources insufficiency input or unbalanced allocation. Chin Health Econ (Zhongguo Wei Sheng **g Ji) 2012; 31(8): 12–15 (in Chinese)

    Google Scholar 

  37. Feng Z. Chinese health care in rural areas. BMJ 2010; 341: c5254

    PubMed  Google Scholar 

  38. KDOQI. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic disease. Am J Kidney Dis 2007; 49(2 Suppl 2): S12–S154

    Google Scholar 

  39. Tuttle KR, Bakris GL, Bilous RW, Chiang JL, de Boer IH, Goldstein-Fuchs J, Hirsch IB, Kalantar-Zadeh K, Narva AS, Navaneethan SD, Neumiller JJ, Patel UD, Ratner RE, Whaley-Connell AT, Molitch ME. Diabetic kidney disease: a report from an ADA Consensus Conference. Am J Kidney Dis 2014; 64(4): 510–533

    PubMed  Google Scholar 

  40. National Clinical Guideline Centre (UK). Chronic Kidney Disease (Partial Update): Early Identification and Management of Chronic Kidney Disease in Adults in Primary and Secondary Care. London: National Institute for Health and Care Excellence (UK). 2014

    Google Scholar 

  41. Zitkus BS. Update on the American Diabetes Association Standards of Medical Care. Nurse Pract 2014; 39(8): 22–32

    PubMed  Google Scholar 

  42. Kanwar YS, Sun L, **e P, Liu FY, Chen S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 2011; 6(1): 395–423

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Lan HY, Chung ACK. Transforming growth factor-β and Smads. Contrib Nephrol 2011; 170: 75–82

    CAS  PubMed  Google Scholar 

  44. Sato Y. The vasohibin family: a novel family for angiogenesis regulation. J Biochem 2013; 153(1): 5–11

    CAS  PubMed  Google Scholar 

  45. Yao XF, Cai D, Quan JJ. Levels and clinical significances of IGF-1, TGF-β and VEGF in patients with type 2 diabetic nephropathy. Med Pharm J Chin PLA (Jie Fang Jun Yi Yao ZaZhi) 2017; 29(6): 78–81 (in Chinese)

    Google Scholar 

  46. Fathy SA, Mohamed MR, Ali M A M, El-Helaly AE, Alattar AT. Influence of IL-6, IL-10, IFN-γ and TNF-α genetic variants on susceptibility to diabetic kidney disease in type 2 diabetes mellitus patients. Biomarkers 2019; 24(1): 43–55

    CAS  PubMed  Google Scholar 

  47. Lu C, Han HD, Mangala LS, Ali-Fehmi R, Newton CS, Ozbun L, Armaiz-Pena GN, Hu W, Stone RL, Munkarah A, Ravoori MK, Shahzad MM, Lee JW, Mora E, Langley RR, Carroll AR, Matsuo K, Spannuth WA, Schmandt R, Jennings NB, Goodman BW, Jaffe RB, Nick AM, Kim HS, Guven EO, Chen YH, Li LY, Hsu MC, Coleman RL, Calin GA, Denkbas EB, Lim JY, Lee JS, Kundra V, Birrer MJ, Hung MC, Lopez-Berestein G, Sood AK. Regulation of tumor angiogenesis by EZH2. Cancer Cell 2010; 18(2): 185–197

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Yeo ES, Hwang JY, Park JE, Choi YJ, Huh KB, Kim WY. Tumor necrosis factor (TNF-α) and C-reactive protein (CRP) are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes. Yonsei Med J 2010; 51(4): 519–525

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Magri CJ, Calleja N, Buhagiar G, Fava S, Vassallo J. Factors associated with diabetic nephropathy in subjects with proliferative retinopathy. Int Urol Nephrol 2012; 44(1): 197–206

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the Higher School “High-end Talent Team Construction” of Liaoning Province (No. [2014]187) and the Natural Science Foundation of Liaoning Province (No. 201602862), Liaoning Province, China.

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Authors and Affiliations

  1. Department of Endocrinology, the First Hospital of China Medical University, Shenyang, 110001, China

    Huiwen Ren, Yang Zhou & Qiuyue Wang

  2. Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China

    Huiwen Ren

  3. Department of Gastroenterology and Endoscopy, the First Hospital of China Medical University, Shenyang, 110001, China

    Can Wu

  4. Department of Endocrinology, the Second Hospital of China Medical University, Shenyang, 110001, China

    Ying Shao

  5. Severe Infection Intensive Care Unit, Affiliated Central Hospital of Shenyang Medical College, Shenyang, 110001, China

    Shuang Liu

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  1. Huiwen Ren
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Correspondence to Qiuyue Wang.

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Huiwen Ren, Can Wu, Ying Shao, Shuang Liu, Yang Zhou, and Qiuyue Wang declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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Ren, H., Wu, C., Shao, Y. et al. Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study. Front. Med. 14, 642–650 (2020). https://doi.org/10.1007/s11684-019-0719-3

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