Year: 2017
Type: dissertation
Abstract: Recent transcriptome studies have elucidated that the human genome is pervasively transcribed and generates thousands of non-protein-coding RNA transcripts (ncRNAs), which are proposed to be involved in a variety of regulatory processes associated with human diseases.Thereby, several studies have shown that ncRNAs play important roles in tumorigenesis, neurological and developmental disorders, cardiovascular diseases, renal, kidney diseases or other disorders, respectively.To date, these studies have focused primarily on profiling microRNAs (miRNAs) expression patterns.However, not much is known about other classes of ncRNAs that are involved in human diseases.Therefore, work focused on the identification of regulatory ncRNAs, in addition to microRNAs, involved in two human diseases:Multiple System Atrophy (MSA) and Chronic Kidney Disease (CKD), respectively.To identify regulatory ncRNAs in an MSA mouse model, differential expression of ncRNAs was investigated by microarray analysis of substantia nigra (SN) and striatum, two brain regions that undergo neurodegeneration at a later stage of the disease in an MSA model.Thereby, in total, 33 differentially expressed microRNAs were identified in striatum and 59 miRNAs in SN.In addition, differential expression of mRNAs was bioinformatically analysed based on RNA-seq and mRNA microarray data from striatum and SN samples, respectively.Subsequently, miRNA-mRNA interactions were computationally predicted and were shown to be involved in specific biological processes linked to MSA.The negatively regulated miRNA-mRNA pairs were associated with immune system processes, in the very early non-symptomatic disease stages of MSA (SN and striatum).The early stages of MSA also showed association with homeostasis and oxidative stress in SN whereas protein handling, metabolism, transmembrane transport, cell death were linked to the striatum, respectively.To identify differentially expressed ncRNAs in CKD, expression analysis was performed by RNAseq from urinary exosomes of CKD patients or healthy controls, respectively.For RNA-seq analysis, we developed a novel computational pipeline, designated as ncRNASeqScan.ncRNASeqScan identifies novel ncRNAs such as miRNAs, tRNAs, tRNA fragments (tRFs), mitochondrial tRNAs, or lincRNAs, respectively.In this analysis, 30 differentially expressed ncRNAs were identified from urinary exosomes as suitable biomarkers for early diagnosis in CKD patients.Employing a cell culture system for CKD demonstrated that urinary exosomes might indeed originate from renal proximal tubular epithelial cells.
Author: Khurana, Rimpi
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7047441799