Dataset Information

Integrative Analysis of miRNA and mRNA Expression Profiles in Calcium Oxalate Nephrolithiasis Rat Model.

ABSTRACT: The microRNA (miRNA) expression profiles and their biological functions in calcium oxalate nephrolithiasis remain unclear. In this study, we investigate the miRNA and mRNA expression profiles of kidney tissues in calcium oxalate stone rats. 16 Sprague Dawley rats were divided into control group and stone-forming group. 24-hour urine samples and kidney tissues were collected for biochemical and histological determination after 4 weeks. MiRNA and mRNA microarray were applied to evaluate the miRNA and mRNA expression profiles. To validate the microarray results, the quantitative real-time PCR (qRT-PCR) was performed. A total of 38 miRNAs and 2728 mRNAs were significantly and differentially expressed in kidney tissues of stone-forming group versus control group. Gene Ontology (GO) analysis revealed that most of the target genes were enriched in terms of oxidation reduction, ion transport, inflammatory response, and response to wounding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of these targets highlights their critical role in cytokine-cytokine receptor interaction, gap junction, and chemokine signaling pathway. Furthermore, the reliability of the microarray-based results was confirmed by using qRT-PCR determination. The miRNA and mRNA expressions in calcium oxalate stone rat kidneys might provide a basis for further research on urolithiasis mechanism.

SUBMITTER: Lan C

PROVIDER: S-EPMC5748115 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Integrative Analysis of miRNA and mRNA Expression Profiles in Calcium Oxalate Nephrolithiasis Rat Model.

Lan Chuangxin C Chen Dong D Liang Xiongfa X Huang Jian J Zeng Tao T Duan Xiaolu X Chen Kang K Lai Yongchang Y Yang Dong D Li Shujue S Jiang Chonghe C Wu Wenqi W

BioMed research international 20171217

The microRNA (miRNA) expression profiles and their biological functions in calcium oxalate nephrolithiasis remain unclear. In this study, we investigate the miRNA and mRNA expression profiles of kidney tissues in calcium oxalate stone rats. 16 Sprague Dawley rats were divided into control group and stone-forming group. 24-hour urine samples and kidney tissues were collected for biochemical and histological determination after 4 weeks. MiRNA and mRNA microarray were applied to evaluate the miRNA ...[more]

PMID: 29392139

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Project description:BackgroundTo explore long-non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) expression profiles and their biological functions in the urine samples in calcium oxalate (CaOx) patients.MethodsFive CaOx kidney stone patients were recruited in CaOx stone group and six healthy people were included as control group, whose midstream morning urine was collected before the patients were given any medicine on admission. After total RNA was extracted from urine, microarray of miRNA, mRNA and lncRNA were applied to explore their expression variation. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to reveal the gene functions of the dysregulated lncRNA-associated competing endogenous RNA (ceRNA) network. Quantitative real-time PCR were performed on HK-2 cells treated with sodium oxalate (NaOx) to further screen out the differentially expression profiles of these RNAs.ResultsA total of nine miRNAs, 883 mRNAs and 1002 lncRNAs were differentially expressed in urine of CaOx patients compared with normal population. GO analysis revealed that most of mRNAs from ceRNA network were enriched in terms of respiratory burst, regulation of mitophagy, and protein kinase regulator activity. KEGG pathway analysis of these genes related to ceRNA network highlight their critical role in pentose phosphate pathway, glyoxylate and dicarboxylate metabolism, and Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. Five miRNAs (miR-6796-3p, miR-30d-5p, miR-3192-3p, miR-518b and miR-6776-3p), four mRNAs (NT5E, CDH4, CLEC14A, CCNL1) and six lncRNAs (lnc-TIGD1L2-3, lnc-KIN-1, lnc-FAM72B-4, lnc-EVI5L-1, lnc-SERPINI1-2, lnc-MB-6) from the HK-2 cells induced by NaOx were consistent with the expression changes of microarray results.ConclusionThe differential expressed miRNAs, mRNAs and lncRNAs may be associated with numerous variations of the signaling pathways or regulation of metabolism and kinase activity, providing potential biomarkers for early diagnosis of urolithiasis and new basis for further research of urolithiasis mechanism.

Project description:Oxidative stress, a well-known cause of stress-induced premature senescence (SIPS), is increased in patients with calcium oxalate (CaOx) kidney stones (KS). Oxalate and calcium oxalate monohydrate (COM) induce oxidative stress in renal tubular cells, but to our knowledge, their effect on SIPS has not yet been examined. Here, we examined whether oxalate, COM, or urine from patients with CaOx KS could induce SIPS and telomere shortening in human kidney (HK)-2 cells, a proximal tubular renal cell line. Urine from age- and sex-matched individuals without stones was used as a control. In sublethal amounts, H2O2, oxalate, COM, and urine from those with KS evoked oxidative stress in HK-2 cells, indicated by increased protein carbonyl content and decreased total antioxidant capacity, but urine from those without stones did not. The proportion of senescent HK-2 cells, as indicated by SA-βgal staining, increased after treatment with H2O2, oxalate, COM, and urine from those with KS. Expression of p16 was higher in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than it was in cells treated with urine from those without stones and untreated controls. p16 was upregulated in the SA-βgal positive cells. Relative telomere length was shorter in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than that in cells treated with urine from those without stones and untreated controls. Transcript expression of shelterin components (TRF1, TRF2 and POT1) was decreased in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS, in which case the expression was highest. Urine from those without KS did not significantly alter TRF1, TRF2, and POT1 mRNA expression in HK-2 cells relative to untreated controls. In conclusion, oxalate, COM, and urine from patients with CaOx KS induced SIPS and telomere shortening in renal tubular cells. SIPS induced by a lithogenic milieu may result from upregulation of p16 and downregulation of shelterin components, specifically POT1, and might contribute, at least in part, to the development of CaOx KS.

Project description:Gastric cancer (GC) is one of the most common types of malignant cancer and is associated with poor prognosis. Although the prognosis of patients with GC is associated with grade, stage and lymph node metastases, these traditional clinical features are inadequate to predict the outcome of GC. Therefore, there has been an increased focus on identifying novel molecular biomarkers for early diagnosis and prognosis, in order to improve outcomes in GC. In the present study, an integrative analysis of microRNA (miRNA) expression profiles, mRNA expression profiles and clinical characteristics was performed in a large cohort of patients with GC in order to identify an integrative prognostic model for improving postoperative risk classification. An integrative mRNA/miRNA signature (IMMIS), comprised of three miRNAs and one mRNA, was identified from a large number of differentially expressed miRNAs and mRNAs using univariate and multivariate Cox regression analysis. The prognostic value of the IMMIS was validated in the discovery cohort, testing cohort and The Cancer Genome Atlas (TCGA) cohort. The present results suggested that the identified signature had a reliable predictive performance and could classify the patients into high- and low-risk groups with significantly different overall survival times. In the discovery cohort, the hazard ratio (HR) was 2.805 with a 95% CI=1.722-4.567 (P<0.001). The median overall survival time as 1.49 vs. 3.85 years. In the testing cohort, the HR was 1.625 with a 95% CI=1.004-2.638 (P=0.039) and the median overall survival time was 2.17 vs. 4.62 years. In the TCGA cohort, the HR was 2.139 with a 95% CI=1.519-3.012 (P<0.001) and the median overall survival time was 1.53 vs. 4.62 years. The IMMIS constituted a reliable independent prognostic factor compared with clinical covariates, including age, sex, grade and stage, as indicated by multivariate and stratified analyses. Furthermore, comparative analysis revealed that the predictive value of the IMMIS was superior to the mRNA-based signature alone. The present results suggested the potential value of the IMMIS as a promising novel biomarker for improving the clinical management of patients with GC.

Dataset Information

Integrative Analysis of miRNA and mRNA Expression Profiles in Calcium Oxalate Nephrolithiasis Rat Model.

Publications

Integrative Analysis of miRNA and mRNA Expression Profiles in Calcium Oxalate Nephrolithiasis Rat Model.

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