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CircNr1h4 regulates the pathological process of renal injury in salt-sensitive hypertensive mice by targeting miR-155-5p.

ABSTRACT: Circular RNAs are a class of widespread and diverse endogenous RNAs that may regulate gene expression in various diseases, but their regulation and function in hypertensive renal injury remain unclear. In this study, we generated ribosomal-depleted RNA sequencing data from normal mouse kidneys and from injured mouse kidneys induced by deoxycorticosterone acetate-salt hypertension and identified at least 4900 circRNA candidates. A total of 124 of these circRNAs were differentially expressed between the normal and injured kidneys. Furthermore, we characterized one abundant circRNA, termed circNr1h4, which is derived from the Nr1h4 gene and significantly down-regulated in the injured kidneys. RNA sequencing data and qPCR analysis also showed many microRNAs and mRNAs, including miR-155-5p and fatty acid reductase 1 (Far1), were differentially expressed between the normal and injured kidney and related to circNr1h4. In vitro, the silencing of circNr1h4 or overexpression of miR-155-5p significantly decreased Far1 levels and increased reactive oxygen species. Mechanistic investigations indicated that circNr1h4 acts as a competing endogenous RNA for miR-155-5p, leading to regulation of its target gene Far1. Our study provides novel insight into the molecular mechanisms underlying kidney injury in hypertension, which will be required to develop therapeutic strategies of targeting circRNAs for hypertensive kidney injury.

SUBMITTER: Lu C

PROVIDER: S-EPMC6991678 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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CircNr1h4 regulates the pathological process of renal injury in salt-sensitive hypertensive mice by targeting miR-155-5p.

Lu Chaosheng C Chen Bicheng B Chen Congcong C Li Haiyan H Wang Dan D Tan Yi Y Weng Huachun H

Journal of cellular and molecular medicine 20191128 2

Circular RNAs are a class of widespread and diverse endogenous RNAs that may regulate gene expression in various diseases, but their regulation and function in hypertensive renal injury remain unclear. In this study, we generated ribosomal-depleted RNA sequencing data from normal mouse kidneys and from injured mouse kidneys induced by deoxycorticosterone acetate-salt hypertension and identified at least 4900 circRNA candidates. A total of 124 of these circRNAs were differentially expressed betwe ...[more]

PMID: 31782248

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Project description:Introduction: Acute graft vs. host disease (aGvHD) is a frequent complication following allogeneic haematopoeitic transplantation (HSCT). Despite recent advances, there are no universally accepted biomarkers to determine development of aGvHD. MicroRNAs miR-146a and miR-155 have been previously associated with aGvHD and show promise as clinically translatable biomarkers. In this study, we performed comprehensive expression profiling of miR-146a, miR-155, and miR-155* expression in aGvHD target tissue and biofluids and relate expression to post-HSCT outcomes. Materials and Methods: MicroRNA expression was assessed by qRT-PCR in gastrointestinal (n = 31) and skin (n = 31) biopsies as well as serum (exploratory cohort n = 34, verification cohort n = 81, diagnostic cohort n = 65) and urine (exploratory cohort n = 30, verification cohort n = 56, diagnostic cohort n = 20) biofluids, including extracellular vesicle (EV) cohorts (serum EV n = 15, urine EV n = 30). Expression was related to aGvHD incidence, severity and overall survival. Results: In GI samples, expression of miR-155 (p = 0.03) and miR-146a (p = 0.03) was higher at aGvHD onset compared to patients with no GvHD. In skin biopsies, expression of miR-155 (p = 0.004) was upregulated in aGvHD patients compared to normal control skin. Expression of miR-146a was higher in aGvHD compared to no aGvHD biopsies (p = 0.002). In serum, miR-155 (p = 0.03) and miR-146a (p = 0.02) expression was higher at day 14 (D14), while in urine expression was elevated at D7 post-HSCT in patients who developed aGvHD compared to those disease-free. This was verified in an independent serum (miR-155 p = 0.005, miR-146a p = 0.003) and urine (miR-155 p = 0.02, miR-146a p = 0.04) cohort, where both microRNAs were also associated with aGvHD by ROC analysis. In serum and urine samples taken at the time of aGvHD symptoms, expression of miR-155 and miR-146a was also elevated (serum miR-155 p = 0.03, miR-146a p < 0.001; urine miR-155 p = 0.02, miR-146a p = 0.02). In contrast, miR-146a and miR-155 were downregulated at D14 in serum EVs and at D7 in urine EVs in patients who developed aGvHD compared to those that remained disease-free, in both an exploratory (serum miR-155 p = 0.02, miR-146a p = 0.06; urine miR-155 p = 0.02, miR-146a p = 0.07) and an independent cohort (serum miR-155 p = 0.01, miR-146a p = 0.02). Conclusions: These results further support a role for miR-155 and miR-146a as non-invasive, clinically relevant biomarkers for aGvHD. However, the link between their involvement in generalized inflammation and in specific pathophysiology requires further investigation at a systemic level.

Project description:BackgroundThe differentiation of stem cells from exfoliated deciduous teeth (SHEDs) into odontoblasts determines the regeneration of dentin-pulp complex. Non-coding RNAs (ncRNAs), including microRNA (miRNA) and long non-coding RNA (lncRNA), participate in many multiple biological processes, but the specific miRNAs involved in odontogenesis are incompletely defined. It was confirmed that lncRNA IGFBP7-AS1 could positively regulate odontogenetic differentiation in SHEDs. To investigate the downstream mechanisms of this process, miR-335-3p and miR-155-5p were found to be closely related with SHED odontogenic differentiation through whole-genome sequencing. The aim of the current study was to determine the role of miR-335-3p/miR-155-5p in IGFBP7-AS1-enhanced SHED differentiation and explore the potential mechanism of IGFBP7-AS1-mediated odontogenesis.MethodsPutative miR-335-3p/miR-155-5p binding sites within IGFBP7-AS1 were identified by bioinformatics analysis, and the binding of miR-335-3p/miR-155-5p to these sites was confirmed by dual-luciferase reporter gene assays. The effects of miR-335-3p/miR-155-5p in odontogenesis were detected by tissue nonspecific alkaline phosphatase staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR) analyses, and western blot testing. The molecular mechanisms of miR-335-3p/miR-155-5p involved in IGFBP7-AS1-mediated odontogenesis were analysed by qRT-PCR and western blot testing.ResultsDual-luciferase reporter gene assays showed that miR-335-3p/miR-155-5p could directly bind to IGFBP7-AS1. MiR-335-3p and miR-155-5p both could down-regulate dentin sialophosphoprotein expression, and both miRNAs could inhibit IGFBP7-AS1-mediated SHED odontogenetic differentiation via suppression of the extracellular signal-regulated kinase (ERK) pathway.ConclusionsBoth miR-335-3p and miR-155-5p were negative regulators to IGFBP7-AS1-enhanced odontogenic differentiation of SHED through suppression of the ERK pathway.

Dataset Information

CircNr1h4 regulates the pathological process of renal injury in salt-sensitive hypertensive mice by targeting miR-155-5p.

Publications

CircNr1h4 regulates the pathological process of renal injury in salt-sensitive hypertensive mice by targeting miR-155-5p.

Similar Datasets

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