Human MiR-4660 Regulates the Expression of Alanine-glyoxylate Aminotransferase and May Be a Biomarker for Idiopathic Oxalosis

Overview

Journal Clin Exp Nephrol

Publisher Springer

Specialty Nephrology

Date 2019 Mar 11

PMID 30852714

Citations 6

Authors

Xin Tu

Yuanyuan Zhao

Qianqian Li

Xiao Yu

Yang Yang

Shumei Shi

Zuochuan Ding

Yan Miao

Zhimiao Zou

Xinqiang Wang

Jipin Jiang

Dunfeng Du

Affiliations

Soon will be listed here.

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.

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