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Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis
Sohyun Jeong1, Jung Mi Oh1, Kook-Hwan Oh2
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Abstract:
Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (<150 pg/mL) and 41 patients had high iPTH (≥150 pg/mL). Total RNA was extracted from whole blood samples. Total RNA from 15 patients (7 and 8 patients in the low and high iPTH groups, respectively) underwent miRNA microarray analysis, and three differentially upregulated (>2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development.
Insights
This study identified miR-3680-5p as a potential biomarker for mineral and bone disorder (MBD) in peritoneal dialysis (PD) patients. Its differential expression links to parathyroid hormone levels and may influence MBD development.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Mineral and bone disorder (MBD) is a common complication in chronic kidney disease (CKD) patients, leading to adverse skeletal changes.
- MicroRNAs (miRNAs) show promise as biomarkers for various diseases, including CKD-MBD.
- Parathyroid hormone (PTH) levels are critical indicators in managing CKD-MBD.
Purpose of the Study:
- To identify specific miRNAs associated with parathyroid hormone (PTH) levels in patients undergoing peritoneal dialysis (PD).
- To investigate the potential role of these miRNAs in the pathogenesis of CKD-MBD.
Main Methods:
- Microarray analysis of whole blood samples from 52 PD patients categorized by intact PTH (iPTH) levels.
- Selection and validation of differentially expressed miRNAs using real-time quantitative PCR (qPCR).
- Bioinformatic analysis (TargetScan, KEGG) to predict miRNA target genes and associated pathways.
Main Results:
- 165 miRNAs were differentially expressed between high and low iPTH groups in PD patients.
- miR-3680-5p was significantly differentially expressed between the low and high iPTH groups (P < 0.05).
- Predicted target genes of miR-3680-5p, including USP6, USP32, USP46, and DLT, are involved in the ubiquitin proteolysis pathway.
Conclusions:
- miR-3680-5p is a potential biomarker for differentiating PTH levels in PD patients.
- The ubiquitin proteolysis pathway, influenced by miR-3680-5p targets, may play a role in CKD-MBD.
- Further research is needed to elucidate the mechanisms linking miR-3680-5p, its targets, and CKD-MBD development.
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