Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients.
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.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Sohyun
S
Jeong
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Jung Mi
JM
Oh
Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Kook-Hwan
KH
Oh
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
In-Wha
IW
Kim
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy; D010450:Endopeptidases / Q000235:genetics; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood*; D010530:Peritoneal Dialysis / Q000379:methods*; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D056910:Republic of Korea; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D055815:Young Adult
D005819:Genetic Markers; C000622412:MIRN3680 microRNA, human; D035683:MicroRNAs; D010281:Parathyroid Hormone; D011518:Proto-Oncogene Proteins; C431363:USP10 protein, human; D010450:Endopeptidases; C562185:ubiquitin-specific peptidase 46, human; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase