Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease.
Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease.
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DOI：
10.1261/rna.058834.116
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
Hüttenhofer A
中科院分区：
文献类型：
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作者：
Khurana R;Ranches G;Schafferer S;Lukasser M;Rudnicki M;Mayer G;Hüttenhofer A
在慢性肾病（CKD）中，肾小球滤过率的下降与发病率和死亡率的增加有关，因此对医疗保健系统构成了重大挑战。虽然组织来源的miRNA和mRNA对CKD进展的贡献已被广泛研究，但对尿外泌体的作用及其与CKD的关联知之甚少。外泌体是小的、膜衍生的内吞囊泡，其有助于细胞与细胞的通讯，并且存在于各种体液中，例如血液或尿液。下一代测序方法已经揭示了外泌体富含非编码RNA，因此在各种人类疾病中表现出作为敏感核酸生物标志物的巨大潜力。因此，在这项研究中，我们的目的是确定尿外泌体ncRNA作为诊断CKD的新生物标志物。由于到目前为止，大多数方法都集中在miRNA类，我们将我们的分析扩展到其他几种非编码RNA类，如tRNA，tRNA片段（tRFs），线粒体tRNA或lincRNA。为了从RNA-seq数据中进行计算识别，我们开发了一种新的计算管道，称为ncRNASeqScan。通过这些分析，我们在CKD患者中鉴定了30种差异表达的ncRNA，这些ncRNA来源于尿外泌体，作为早期诊断的合适生物标志物。因此，miRNA-181 a似乎是最稳健和稳定的潜在生物标志物，与健康对照相比，在CKD患者的外泌体中显著降低约200倍。使用CKD的细胞培养系统表明，尿外泌体可能确实来源于肾近端小管上皮细胞。
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.