MicroRNA-206 and its down-regulation of Wilms’Tumor-1 dictate podocyte health in adriamycin-induced nephropathy

Guo, Na; Guo, Jing; Su, Dongfang

doi:10.3109/0886022x.2016.1165119

Cited by 13 publications

(9 citation statements)

References 22 publications

(25 reference statements)

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“…However, the onco-driving role of SYNPO needs more evidence to support it, because there are some controversial findings. For example, miR-206 was reported to be up-regulated in murine nephropathy, which causes severe podocyte injury and inhibits the expression of WT1 and SYNPO (Guo et al, 2016). Our results, for the first time, highlight that SYNPO can be a risk carcinogenic gene in WT.…”

Section: Discussionmentioning

confidence: 56%

Identification of key carcinogenic genes in Wilms’ tumor

Liu

Xiao

et al. 2021

Genes Genet. Syst.

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This study aimed to probe carcinogenic genes and pathways associated with Wilms' tumor (WT) onset and malignancy progression. After screening, three datasets acquired from the Gene Expression Omnibus database were analyzed. Differentially expressed genes (DEGs) were identified and GO functional enrichment, KEGG pathway enrichment and protein-protein interaction (PPI) were analyzed. The DEGs with top fold change values or top protein interaction scores were used to analyze overall survival based on the TARGET WT dataset. Together, 866 up-regulated genes in GDS1791, 585 up-regulated genes in GDS2010, and 277 down-regulated genes in GDS4802 were found, from which 46 key DEGs were selected for further analysis. In the PPI network, hub positions included COL5A1, COL4A1, ARPP21, SPARCL1, CD86, LY96 and PPP1R12B. The top DEGs (ARPP21, SYNPO, PRRC2B, PPP1R12B, EFCAB2 and LY96) were selected for survival analysis, and they consistently showed a significantly positive correlation with poor survival. Together, five key carcinogenic genes (SYNPO, PRRC2B, PPP1R12B, EFCAB2 and LY96) were highly associated with WT onset and patient survival. These risk genes, interaction networks and enrichments should improve our understanding of the complex molecular mechanisms in WT development and help clinical applications.

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Section: Discussionmentioning

confidence: 56%

Identification of key carcinogenic genes in Wilms’ tumor

Liu

Xiao

et al. 2021

Genes Genet. Syst.

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“…Consistent with this view, another study demonstrates that miR-206 is upregulated in ADR models and promotes podocyte injury via downregulation of WT1. 38 In addition, miRNA-193a is implicated in mediating WT1 depletion in FSGS, 19 supporting the possibility that targeting WT1 for depletion by miRNAs is common feature of proteinuric kidney diseases.…”

Section: Discussionmentioning

confidence: 95%

MicroRNA‐466o‐3p mediates β‐catenin‐induced podocyte injury by targeting Wilms tumor 1

Chen

Wang

et al. 2020

The FASEB Journal

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Podocytes are highly specialized cells that play an essential role in maintaining the integrity and function of the glomerular filtration barrier. Wilms tumor 1 (WT1) and β-catenin are two master regulators that play opposing roles in podocyte biology and mutually antagonize each other. However, exactly how β-catenin inhibits WT1 remains incompletely understood. In this study, we demonstrated the role of miR-466o-3p in mediating β-catenin-triggered podocyte injury by targeting WT1. The expression of miR-466o-3p was upregulated in cultured podocytes after β-catenin activation and in glomerular podocytes in adriamycin (ADR) nephropathy, remnant kidney after 5/6 renal ablation, and diabetic kidney disease. Bioinformatics analysis and luciferase reporter assay confirmed that miR-466o-3p directly targeted WT1 mRNA. Furthermore, overexpression of miR-466o-3p downregulated WT1 protein and promoted podocyte injury in vitro. Conversely, inhibition of miR-466o-3p alleviated β-catenin-induced podocyte dysfunction. In mouse model of ADR nephropathy, overexpression of miR-466o-3p inhibited WT1, aggravated podocytes injury and deteriorated proteinuria. In contrast, inhibition of renal miR-466o-3p by antagomiR, either prior to or after ADR injection, substantially restored WT1, alleviated podocytes injury and reduced renal fibrosis. These studies reveal a critical role for miR-466o-3p, a novel microRNA that has not been characterized previously, in mediating β-catenin-triggered WT1 inhibition. Our findings also uncover a new pathogenic mechanism by which β-catenin promotes podocyte injury and proteinuria in glomerular diseases.

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“…Wu et al also demonstrated that miR-30s were consistently downregulated in podocytes of FSGS patients and PANtreated rats, and identified that downregulation of miR-30s results in calcium/calcineurin signaling activation, thus leading to podocyte injury in FSGS (Wu et al, 2015). In addition, other studies have also reported the involvement of some other dysregulated miRNAs in FSGS, such as miR-135a (Yang et al, 2017), miR-155 (Ramezani et al, 2015), miR-206 (Guo et al, 2016), miR-150 (Qi et al, 2020), miR-106a (Xiao et al, 2018) and miR-146-5p (Williams et al, 2022).…”

Section: Mirnas In Focal Segmental Glomerulosclerosismentioning

confidence: 93%

Pathogenic Role of MicroRNA Dysregulation in Podocytopathies

Liu

Chen

et al. 2022

Front. Physiol.

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MicroRNAs (miRNAs) participate in the regulation of various important biological processes by regulating the expression of various genes at the post-transcriptional level. Podocytopathies are a series of renal diseases in which direct or indirect damage of podocytes results in proteinuria or nephrotic syndrome. Despite decades of research, the exact pathogenesis of podocytopathies remains incompletely understood and effective therapies are still lacking. An increasing body of evidence has revealed a critical role of miRNAs dysregulation in the onset and progression of podocytopathies. Moreover, several lines of research aimed at improving common podocytopathies diagnostic tools and avoiding invasive kidney biopsies have also identified circulating and urine miRNAs as possible diagnostic and prognostic biomarkers for podocytopathies. The present review mainly aims to provide an updated overview of the recent achievements in research on the potential applicability of miRNAs involved in renal disorders related to podocyte dysfunction by laying particular emphasis on focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous nephropathy (MN), diabetic kidney disease (DKD) and IgA nephropathy (IgAN). Further investigation into these dysregulated miRNAs will not only generate novel insights into the mechanisms of podocytopathies, but also might yield novel strategies for the diagnosis and therapy of this disease.

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MicroRNA-206 and its down-regulation of Wilms’Tumor-1 dictate podocyte health in adriamycin-induced nephropathy

Cited by 13 publications

References 22 publications

Identification of key carcinogenic genes in Wilms’ tumor

Identification of key carcinogenic genes in Wilms’ tumor

MicroRNA‐466o‐3p mediates β‐catenin‐induced podocyte injury by targeting Wilms tumor 1

Pathogenic Role of MicroRNA Dysregulation in Podocytopathies

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