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PLoS One. 2017;12(2):e0170535.

Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients.

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제1저자 정소현 · 교신저자 오국환, 김인화

소속 (2)
  1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
  2. Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, 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.

Figures

Fig 1
Fig 1 Volcano plot for differentially expressed miRNAs in patients with low (<150 pg/mL) and high (≥150 pg/mL) iPTH levels.
Fig 2
Fig 2 Heat map illustrating miRNAs profiles in patients with low (<150 pg/mL) and high (≥150 pg/mL) iPTH levels. The log2 values were calculated for each sample by normalizing to the count number of reads alone. The heat map analysis was performed by using Cluster 3.0 with the Euclidean distance algorithm and average linkage (Padj <0.05 and log2 fold change >2). Group 1: iPTH < 150 pg/mL, Group 2: iPTH ≥ 150 pg/mL
Fig 3
Fig 3 Association between iPTH level and upregulation of expression of three miRNAs in 52 PD patients.

그림 출처: PubMed Central 공개 논문 (PMC5289431)

Conflict of interest statement

The authors have declared that no competing interests exist.

그 밖의 정보
출판 형태
Journal Article
저널
PloS one · eISSN 1932-6203
전자 출판
2017-02-02
MeSH
Adult · Aged · Cardiovascular Diseases / epidemiology · Chronic Kidney Disease-Mineral and Bone Disorder / epidemiology / mortality / therapy · Endopeptidases / genetics · Female · Fractures, Bone / epidemiology · Genetic Markers / genetics · Humans · Male · MicroRNAs / biosynthesis / genetics · Middle Aged · Oligonucleotide Array Sequence Analysis · Parathyroid Glands / metabolism · Parathyroid Hormone / blood · Peritoneal Dialysis / methods · Prospective Studies · Proto-Oncogene Proteins / genetics · Real-Time Polymerase Chain Reaction · Republic of Korea · Ubiquitin Thiolesterase / genetics · Young Adult
Substances
Genetic Markers · MIRN3680 microRNA, human · MicroRNAs · Parathyroid Hormone · Proto-Oncogene Proteins · USP10 protein, human · Endopeptidases · ubiquitin-specific peptidase 46, human · USP6 protein, human · Ubiquitin Thiolesterase
참고문헌
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