Analysis Of Transcribed Ultra-conserved Regions Expression In Peripheral Blood Mononuclear Cells Of Uremia Patients

Background:Uremia is not a single disease, but is a self-poisoning syndrome due to metabolites and other toxic substances accumulate in the body by kidney failure. It is the manifestation of the most serious renal failure, the stage V of chronic kidney disease. At present, the diagnosis of uremia can be implemented from clinical symptoms, laboratory examinations or image analysis. It is the terminal stage of chronic renal failure and requires renal replacement therapy, such as hemodialysis or kidney transplantation. In current clinical practice, the diagnosis of uremia and determination of the indicators for renal replacement therapy still use water-soluble small molecules, but uremic patients have a poor prognosis. There is a non-coding gene regions, which is about 200-779 bp of sequence in the human, mouse and rat genes. It is highly conserved, so it is called ultra-conserved region. UCR. It is found in the fragile sites or gene regions of tumor. Transcribed ultraconserved regions (T-UCRs) are the special long non-coding RNAs (ncRNAs) and coded by UCRs. In the human genome, T-UCRs are transcribed from 481 ultraconserved regions and they will alter the expression patterns in the cancers, for example liver cancer, colon cancer, neuroblastoma, etc. T-UCRs involved in cancer biology and tumorigenesis, and may be used as disease diagnosis, prognosis and prediction of indicators, and a new class of therapeutic targets.Objective:There are many researches on complication of uremia and hemodialysis. But there is few research on the pathogenesis of uremia, and its specificity biomarker is still not found. The association between uemia and T-UCRs expression have not been studied yet. The uremia patients requires dialysis or kidney transplantation and need to take long-term medicine. The body and mind of uremia patients are not only under a lot of pressure, but also a heavier economic burden. Therefore, in this paper we use the T-UCR microarray to analyse the ultra-conserved regions expression of peripheral blood mononuclear cells of uremia patients, comparison with healthy controls to find differential expressed T-UCRs and investigate the correlation of those T-UCRs with uremia on the gene transcription level. Further understanding the pathogenesis and finding the biomarkers of uremia.Methods:1. Analysis of transcribed ultra-conserved regions expression in peripheral blood mononuclear cells of 15 uemia ptients and 15 healthy controls by T-UCR microarray techonology.2. Analysis of the differential expression of T-UCRs in uremic patients and healthy controls by hierarchical clustering analysis.3. Analysis of the biological function of the differential expressed T-UCRs by GO analysis.4. Analysis of the relevant pathways of the differential expressed T-UCRs by pathway analysis.Results:Through fold change filter and hierarchical clustering analysis, there were 21 T-UCRs up-regulated and 49 T-UCRs down-regulated of.potentional T-UCRs,311 T-UCRs up-regulated and 330 T-UCRs down-regulated of T-UCRs, which had regulated fuction for RNA transcripts (LncRNAs and mRNAs) whose transcription range overlap UCRs and 181 T-UCRs up-regulated and 339 T-UCRs down-regulated of T-UCRs, which had regulated fuction for UCR-proximal genes in the uremia patients compared with the healthy controls. Through GO analysis and pathway analysis, selecting 6 genes, RP11-369F10.3, HNRPDL, SNORA74A (p=1.115E-17) RBFOX2 (p=1.865E-22), SNORD90 (p=0.00211), FAM24B (p=1.27E-03) for candidate genes. They were significant expression. RP11-369F10.3, SNORA74A, SNORD90 were up-regulated, HNRPDL, RBFOX2 and FAM24B were down-regulated.Conclusion:There were significant alterations of transcribed ultra-conserved regions expression in uremia patients compared with the healthy controls. These significant alterations may help to explain the pathogenesis in uremia patients. These T-UCRs and candidate genes may be the potential biomarkers or therapeutic targets of uremia.