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Endocrine

pp 1–8 | Cite as

MIR4532 gene variant rs60432575 influences the expression of KCNJ11 and the sulfonylureas-stimulated insulin secretion

  • Zhang-Ren Chen
  • Fa-Zhong He
  • Mou-Ze Liu
  • Jin-Lei Hu
  • Heng Xu
  • Hong-Hao Zhou
  • Wei ZhangEmail author
Original Article
  • 224 Downloads

Abstract

Purpose

Diabetes mellitus is a major chronic disease and causes over one million deaths. KCNJ11 genetic polymorphisms influence the response of first-line oral antidiabetic agent sulfonylureas. Hsa-miR-4532 correlates with diabetic nephropathy and has a high abundance in urine. MIR4532 rs60452575 G>A variant changes the mature sequence of hsa-miR-4532. We studied whether the genetic polymorphisms of MIR4532 rs60452575 would influence KCNJ11 expression and sulfonylurea-stimulated insulin secretion or not.

Methods

To estimate the influence that rs60452575 G>A variant has on the interaction of hsa-miR-4532 and KCNJ11, we constructed a pmirGLO vector containing 3′ UTR of KCNJ11 and co-transfected it with wild-type and mutant hsa-miR-4532 mimics into HEK293 cells; and we overexpressed wild-type and mutant hsa-miR-4532 mimics into HEK293 cells and MIN6 cells to access its effects on KCNJ11 expression and response of sulfonylureas.

Results

MIR4532 rs60452575 G>A variant appeared to disrupt the repression of KCNJ11 expression in both cell lines, and reduce the sulfonylurea-stimulated insulin secretion by breaking the binding of the hsa-miR-4532 to 3′ UTR of KCNJ11 in MIN6 cells.

Conclusions

Our study indicates that MIR4532 rs60452575 variant influences KCNJ11 expression and sulfonylurea response. It might be a potential predictive factor of sulfonylureas therapy.

Keywords

MicroRNA Polymorphism KCNJ11 Diabetes Sulfonylureas Insulin 

Notes

Acknowledgements

This research was supported by grants from the National Key Research and Development Program (Nos. 2016YFC0905000, 2016YFC0905001), National High Technology Research and Development Program of China, “863” Project (No. 2012AA02A518), National Natural Science Foundation of China (Nos. 81522048, 81573511, 81273595), Innovation Driven Project of Central South University (No. 2016CX024), and Central South University Innovation Foundation for Postgraduate (2016zzts518).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    GBD, 2016 Causes of Death Collaborators: Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1151–1210 (2017)CrossRefGoogle Scholar
  2. 2.
    International Diabetes Federation. IDF Diabetes Atlas, update 2017. 8th edn (2017) https://www.idf.org/e-library/epidemiology-research/diabetes-atlas.html
  3. 3.
    W. Yang, J. Lu, J. Weng, Prevalence of diabetes among men and women in China. N. Engl. J. Med. 362, 1090–1101 (2010)CrossRefGoogle Scholar
  4. 4.
    American Diabetes Association, Diagnosis and classification of diabetes mellitus. Diabetes Care 37(Suppl 1), S81–S90 (2014)CrossRefGoogle Scholar
  5. 5.
    H. Zhang, P. Bu, Y.H. Xie, Effect of repaglinide and gliclazide on glycaemic control, early-phase insulin secretion and lipid profiles in. Chin. Med. J. (Engl.). 124, 172–176 (2011)PubMedGoogle Scholar
  6. 6.
    A.P. Babenko, M. Vaxillaire, Mechanism of KATP hyperactivity and sulfonylurea tolerance due to a diabetogenic mutation in L0 helix of sulfonylurea receptor 1 (ABCC8). FEBS Lett. 585, 3555–3559 (2011)CrossRefGoogle Scholar
  7. 7.
    A.E. Pontiroli, A. Calderara, G. Pozza, Secondary failure of oral hypoglycaemic agents: frequency, possible causes, and management. Diabetes/Metab. Rev. 10, 31–43 (1994)CrossRefGoogle Scholar
  8. 8.
    E.R. Pearson, I. Flechtner, P.R. Njolstad, Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N. Engl. J. Med. 355, 467–477 (2006)CrossRefGoogle Scholar
  9. 9.
    G. Sesti, E. Laratta, M. Cardellini, The E23K variant of KCNJ11 encoding the pancreatic β-cell adenosine 5′-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 91, 2334–2339 (2006)CrossRefGoogle Scholar
  10. 10.
    A.E. El-Sisi, S.K. Hegazy, S.S. Metwally, Effect of genetic polymorphisms on the development of secondary failure to sulfonylurea in egyptian patients with type 2 diabetes. Ther. Adv. Endocrinol. Metab. 2, 155–164 (2011)CrossRefGoogle Scholar
  11. 11.
    D.P. Bartel, MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009)CrossRefGoogle Scholar
  12. 12.
    S. Li, G. Yang, Development of cystathionine gamma-lyase-specific microRNAs. Sci. Bull. 60, 503–510 (2015)CrossRefGoogle Scholar
  13. 13.
    M. Cardenas-Gonzalez, A. Srivastava, M. Pavkovic, Identification, confirmation, and replication of novel urinary microRNA biomarkers in lupus nephritis and diabetic nephropathy. Clin. Chem. 63, 1515–1526 (2017)CrossRefGoogle Scholar
  14. 14.
    W. Gong, D. Xiao, G. Ming, Type 2 diabetes mellitus-related genetic polymorphisms in microRNAs and microRNA target sites. J. Diabetes 6, 279–289 (2014)CrossRefGoogle Scholar
  15. 15.
    M. Skelin, M. Rupnik, A. Cencic, Pancreatic beta cell lines and their applications in diabetes mellitus research. ALTEX 27, 105–113 (2010)CrossRefGoogle Scholar
  16. 16.
    Y. Tu, X. Gao, G. Li, MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res. 73, 6046–6055 (2013)CrossRefGoogle Scholar
  17. 17.
    J.-h Yuan, F. Yang, F. Wang, A.L. Noncoding, RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 25, 666–681 (2014)CrossRefGoogle Scholar
  18. 18.
    S.-L. Ding, J.-X. Wang, J.-Q. Jiao, A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its ability to regulate the puma protein in apoptosis. J. Biol. Chem. 288, 26865–26877 (2013)CrossRefGoogle Scholar
  19. 19.
    S. A. Kozomara, Griffiths-Jones: miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42, D68–D73 (2014)CrossRefGoogle Scholar
  20. 20.
    R.J. Sam Griffiths-Jones, Grocock, Stijn van Dongen, miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140–D144 (2006)CrossRefGoogle Scholar
  21. 21.
    L.-F. Jia, Y.-F. Zheng, M.-Y. Lyu, miR-29b upregulates miR-195 by targeting DNMT3B in tongue squamous cell carcinoma. Sci. Bull. 61, 212–219 (2016)CrossRefGoogle Scholar
  22. 22.
    P. Proks, F. Reimann, N. Green, Sulfonylurea stimulation of insulin secretion. Diabetes 51, S368–S376 (2002)CrossRefGoogle Scholar
  23. 23.
    H. Zeng, M. Guo, T. Zhou, An isogenic human ESC platform for functional evaluation of genome-wide-association-study-identified diabetes genes and drug discovery. Cell Stem Cell 19, 326–340 (2016).CrossRefGoogle Scholar
  24. 24.
    A. Bhattacharya, J.D. Ziebarth, Y. Cui, PolymiRTS Database 3.0: linking polymorphisms in microRNAs and their target sites with human diseases and biological pathways. Nucleic Acids Res. 42, D86–D91 (2014)CrossRefGoogle Scholar
  25. 25.
    J. Kruger, M. Rehmsmeier, RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res. 34, W451–W454 (2006)CrossRefGoogle Scholar
  26. 26.
    M. Chen, C. Hu, W. Jia, Pharmacogenomics of glinides. Pharmacogenomics 16, 45–60 (2015)CrossRefGoogle Scholar
  27. 27.
    H.C. Martin, S. Wani, A.L. Steptoe, Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs. Genome Biol. 15, R51 (2014)CrossRefGoogle Scholar
  28. 28.
    J. Song, Y. Yang, F. Mauvais-Jarvis, Y.-P. Wang, T. Niu, KCNJ11, ABCC8 and TCF7L2 polymorphisms and the response to sulfonylurea treatment in patients with type 2 diabetes: a bioinformatics assessment. BMC Med. Genet. 18, 64 (2017)CrossRefGoogle Scholar
  29. 29.
    J. Luo, L. Zhao, A.Y. Chen, TCF7L2 variation and proliferative diabetic retinopathy. Diabetes 62, 2613–2617 (2013)CrossRefGoogle Scholar
  30. 30.
    B. Yang, G. Zhai, Y. Gong, Depletion of insulin receptors leads to beta-cell hyperplasia in zebrafish. Sci. Bull. 62, 486–492 (2017)CrossRefGoogle Scholar
  31. 31.
    X. Kong, X. Zhang, Q. Zhao, Obesity-related genomic loci are associated with type 2 diabetes in a Han Chinese population. PLoS ONE 9, 1–9 (2014)Google Scholar
  32. 32.
    M.A. Daniels, C. Kan, D.M. Willmes, Pharmacogenomics in type 2 diabetes: oral antidiabetic drugs. Pharmacogenomics J. 16, 399–410 (2016)CrossRefGoogle Scholar
  33. 33.
    K. Zhou, H.K. Pedersen, A.Y. Dawed, Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery. Nat. Rev. Endocrinol. 12, 337–346 (2016)CrossRefGoogle Scholar
  34. 34.
    Y. He, Y. Ding, B. Liang, A systematic study of dysregulated microRNA in type 2 diabetes mellitus. Int. J. Mol. Sci. 18, 1–23 (2017)Google Scholar
  35. 35.
    J.M. Wang, J. Tao, D.D. Chen, MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus. Arterioscler. Thromb. Vasc. Biol. 34, 99–109 (2014)CrossRefGoogle Scholar
  36. 36.
    C. Ciccacci, D.D. Fusco, L. Cacciotti, MicroRNA genetic variations: association with type 2 diabetes. Acta Diabetol. 50, 867–872 (2013)CrossRefGoogle Scholar
  37. 37.
    X. Wang, W. Li, L. Ma, F. Ping, J. Liu, X. Wu, J. Mao, X. Wang, M. Nie, Investigation of miRNA-binding site variants and risk of gestational diabetes mellitus in Chinese pregnant women. Acta Diabetol. 54, 309–316 (2017)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Zhang-Ren Chen
    • 1
    • 2
    • 3
  • Fa-Zhong He
    • 1
    • 2
    • 4
  • Mou-Ze Liu
    • 1
    • 2
    • 5
  • Jin-Lei Hu
    • 1
    • 2
    • 4
  • Heng Xu
    • 6
  • Hong-Hao Zhou
    • 1
    • 2
    • 4
  • Wei Zhang
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Clinical PharmacologyXiangya Hospital, Central South UniversityChangshaChina
  2. 2.Institute of Clinical Pharmacology, Central South UniversityHunan Key Laboratory of PharmacogeneticsChangshaChina
  3. 3.Department of PharmacyChildren’s Hospital of Jiangxi ProvinceNanchangChina
  4. 4.National Clinical Research Center for Geriatric Disorders, Xiangya HospitalCentral South UniversityChangshaChina
  5. 5.Department of Pharmacy, the Second Xiangya HospitalCentral South UniversityChangshaChina
  6. 6.State Key Laboratory of BiotherapySichuan UniversityChengduChina

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