PMID- 27872161 OWN - NLM STAT- MEDLINE DCOM- 20170907 LR - 20220409 IS - 1469-9001 (Electronic) IS - 1355-8382 (Print) IS - 1355-8382 (Linking) VI - 23 IP - 2 DP - 2017 Feb TI - Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease. PG - 142-152 LID - 10.1261/rna.058834.116 [doi] AB - In chronic kidney disease (CKD), the decline in the glomerular filtration rate is associated with increased morbidity and mortality and thus poses a major challenge for healthcare systems. While the contribution of tissue-derived miRNAs and mRNAs to CKD progression has been extensively studied, little is known about the role of urinary exosomes and their association with CKD. Exosomes are small, membrane-derived endocytic vesicles that contribute to cell-to-cell communication and are present in various body fluids, such as blood or urine. Next-generation sequencing approaches have revealed that exosomes are enriched in noncoding RNAs and thus exhibit great potential for sensitive nucleic acid biomarkers in various human diseases. Therefore, in this study we aimed to identify urinary exosomal ncRNAs as novel biomarkers for diagnosis of CKD. Since up to now most approaches have focused on the class of miRNAs, we extended our analysis to several other noncoding RNA classes, such as tRNAs, tRNA fragments (tRFs), mitochondrial tRNAs, or lincRNAs. For their computational identification from RNA-seq data, we developed a novel computational pipeline, designated as ncRNASeqScan. By these analyses, in CKD patients we identified 30 differentially expressed ncRNAs, derived from urinary exosomes, as suitable biomarkers for early diagnosis. Thereby, miRNA-181a appeared as the most robust and stable potential biomarker, being significantly decreased by about 200-fold in exosomes of CKD patients compared to healthy controls. Using a cell culture system for CKD indicated that urinary exosomes might indeed originate from renal proximal tubular epithelial cells. CI - (c) 2017 Khurana et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. FAU - Khurana, Rimpi AU - Khurana R AD - Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria. FAU - Ranches, Glory AU - Ranches G AD - Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria. FAU - Schafferer, Simon AU - Schafferer S AD - Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria. FAU - Lukasser, Melanie AU - Lukasser M AD - Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria. FAU - Rudnicki, Michael AU - Rudnicki M AUID- ORCID: 0000-0002-7896-2600 AD - Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, 6020 Innsbruck, Austria. FAU - Mayer, Gert AU - Mayer G AD - Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, 6020 Innsbruck, Austria. FAU - Huttenhofer, Alexander AU - Huttenhofer A AD - Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria. AD - i-med GenomeSeq Core, 6020 Innsbruck, Austria. LA - eng PT - Journal Article DEP - 20161121 PL - United States TA - RNA JT - RNA (New York, N.Y.) JID - 9509184 RN - 0 (Biomarkers) RN - 0 (MIrn181 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Mitochondrial) RN - 63231-63-0 (RNA) RN - 9014-25-9 (RNA, Transfer) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers/urine MH - Case-Control Studies MH - Early Diagnosis MH - Epithelial Cells/*metabolism/pathology MH - Exosomes/*chemistry/metabolism MH - Female MH - Glomerular Filtration Rate MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Kidney Tubules, Proximal/*metabolism/pathology MH - Male MH - MicroRNAs/*urine MH - Middle Aged MH - Molecular Sequence Annotation MH - RNA/urine MH - RNA, Long Noncoding/urine MH - RNA, Mitochondrial MH - RNA, Transfer/urine MH - Renal Insufficiency, Chronic/*diagnosis/pathology/urine MH - Sequence Analysis, RNA MH - Severity of Illness Index PMC - PMC5238789 OTO - NOTNLM OT - chronic kidney disease OT - lincRNAs OT - miRNAs OT - ncRNAs OT - sequencing OT - tRFs OT - tRNAs OT - urinary exosomes EDAT- 2016/11/23 06:00 MHDA- 2017/09/08 06:00 PMCR- 2017/02/01 CRDT- 2016/11/23 06:00 PHST- 2016/08/23 00:00 [received] PHST- 2016/11/08 00:00 [accepted] PHST- 2016/11/23 06:00 [pubmed] PHST- 2017/09/08 06:00 [medline] PHST- 2016/11/23 06:00 [entrez] PHST- 2017/02/01 00:00 [pmc-release] AID - rna.058834.116 [pii] AID - RA [pii] AID - 10.1261/rna.058834.116 [doi] PST - ppublish SO - RNA. 2017 Feb;23(2):142-152. doi: 10.1261/rna.058834.116. Epub 2016 Nov 21.