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Human MiR-4660 regulates the expression of alanine–glyoxylate aminotransferase and may be a biomarker for idiopathic oxalosis

  • Xin Tu
  • Yuanyuan Zhao
  • Qianqian Li
  • Xiao Yu
  • Yang Yang
  • Shumei Shi
  • Zuochuan Ding
  • Yan Miao
  • Zhimiao Zou
  • Xinqiang Wang
  • Jipin Jiang
  • Dunfeng DuEmail author
Original article
  • 34 Downloads

Abstract

Background

Dysfunction of oxalate synthesis can cause calcium oxalate stone disease and inherited primary hyperoxaluria (PH) disorders. PH type I (PH1) is one of the most severe hyperoxaluria disorders, which results in urolithiasis, nephrocalcinosis, and end-stage renal disease. Here, we sought to determine the role of microRNAs in regulating AGXT to contribute to the pathogenesis of mutation-negative idiopathic oxalosis.

Methods

We conducted bioinformatics to search for microRNAs binding to AGXT, and examined the expression of the highest hit (miR-4660) in serum samples of patients with oxalosis, liver tissue samples, and determined the correlation and regulation between the microRNA and AGXT in vitro.

Results

MiR-4660 expression was downregulated in patients with oxalosis compared with healthy controls (84.03 copies/µL vs 33.02 copies/µL, P < 0.0001). Moreover, miR-4660 epigenetically decreased the expression of AGT in human liver tissues (Rho = − 0543, P = 0.037). Overexpression of miR-4660 in HepG2 and L02 cell lines led to dysregulation of AGXT at both the mRNA (by 71% and 81%, respectively; P < 0.001) and protein (by 49% and 42%, respectively; P < 0.0001) levels. We confirmed the direct target site of miR-4660 binding to the 3′UTR of AGXT by a luciferase assay.

Conclusion

MiR-4660 is probably a new biomarker for mutation-negative idiopathic oxalosis by regulating the post-transcription of AGXT, providing a potential treatment target of mutation-negative idiopathic oxalosis.

Keywords

Idiopathic oxalosis Primary hyperoxaluria MicroRNA Epigenetic regulation AGXT 

Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Nos. 91439109, 81700300, 81870176 and 91439109) and the Program for New Century Excellent Talents at the University of China (NCET-11-0181).

Author contributions

XT and DD designed the study. YZ, QL, XY and SS performed the experiments and statistical analysis. YY, ZD, YM, ZZ, XW and JJ collected the samples and took part in finishing the experiments.

Compliance with ethical standards

Conflict of interest

All authors do not have any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within 3 years.

Human and animal rights

This study was approved by the appropriate local institutional review boards on human subject research at the Tongji Hospital of Huazhong University of Science and Technology (IRB ID: TJ-C20160114) and conformed to the guidelines set forth by the Declaration of Helsinki.

Informed consent

Written informed consent was obtained from all participants.

Supplementary material

10157_2019_1723_MOESM1_ESM.pdf (174 kb)
Supplementary material 1 (PDF 173 KB)
10157_2019_1723_MOESM2_ESM.docx (20 kb)
Supplementary material 2 (DOCX 19 KB)

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  • Xin Tu
    • 1
  • Yuanyuan Zhao
    • 2
    • 3
    • 4
  • Qianqian Li
    • 1
  • Xiao Yu
    • 5
  • Yang Yang
    • 2
    • 3
    • 4
  • Shumei Shi
    • 1
  • Zuochuan Ding
    • 2
    • 3
    • 4
  • Yan Miao
    • 2
    • 3
    • 4
  • Zhimiao Zou
    • 2
    • 3
    • 4
  • Xinqiang Wang
    • 2
    • 3
    • 4
  • Jipin Jiang
    • 2
    • 3
    • 4
  • Dunfeng Du
    • 2
    • 3
    • 4
    Email author
  1. 1.Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X InstituteHuazhong University of Science and TechnologyWuhanChina
  2. 2.Institute of Organ Transplantation, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Key Laboratory of Organ TransplantationMinistry of EducationWuhanChina
  4. 4.Key Laboratory of Organ TransplantationMinistry of HealthWuhanChina
  5. 5.Institute of Urology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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