<i>miR‐452</i> promotes cell metastasis and the epithelial to mesenchymal by targeting <i>SOX7</i> in clear‐cell renal‐cell carcinoma

Liu, Feng; Guo, Li; Xin, Guangda; Wang, Zhixin

doi:10.1002/jcb.28125

Cited by 5 publications

(3 citation statements)

References 40 publications

(60 reference statements)

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“…4E ), suggesting that Sox7 deficiency in the endocardium did affect ECM formation. Since proliferation contributes to EndMT and Sox7 is an important regulator of cell proliferation 21 , we examined the effect of Sox7 inactivation on proliferation of endocardial cells using immunofluorescence, and found that the number of KI67-positive endocardial cells in Nfatc1 Cre;Sox7 fl/fl cushions decreased sharply compared with those in controls (Fig. 4F ).…”

Section: Resultsmentioning

confidence: 99%

The transcription factor Sox7 modulates endocardiac cushion formation contributed to atrioventricular septal defect through Wnt4/Bmp2 signaling

et al. 2021

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Cardiac septum malformations account for the largest proportion in congenital heart defects. The transcription factor Sox7 has critical functions in the vascular development and angiogenesis. It is unclear whether Sox7 also contributes to cardiac septation development. We identified a de novo 8p23.1 deletion with Sox7 haploinsufficiency in an atrioventricular septal defect (AVSD) patient using whole exome sequencing in 100 AVSD patients. Then, multiple Sox7 conditional loss-of-function mice models were generated to explore the role of Sox7 in atrioventricular cushion development. Sox7 deficiency mice embryos exhibited partial AVSD and impaired endothelial to mesenchymal transition (EndMT). Transcriptome analysis revealed BMP signaling pathway was significantly downregulated in Sox7 deficiency atrioventricular cushions. Mechanistically, Sox7 deficiency reduced the expressions of Bmp2 in atrioventricular canal myocardium and Wnt4 in endocardium, and Sox7 binds to Wnt4 and Bmp2 directly. Furthermore, WNT4 or BMP2 protein could partially rescue the impaired EndMT process caused by Sox7 deficiency, and inhibition of BMP2 by Noggin could attenuate the effect of WNT4 protein. In summary, our findings identify Sox7 as a novel AVSD pathogenic candidate gene, and it can regulate the EndMT involved in atrioventricular cushion morphogenesis through Wnt4–Bmp2 signaling. This study contributes new strategies to the diagnosis and treatment of congenital heart defects.

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Section: Resultsmentioning

confidence: 99%

The transcription factor Sox7 modulates endocardiac cushion formation contributed to atrioventricular septal defect through Wnt4/Bmp2 signaling

et al. 2021

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“…miR-452 is an evolutionarily conserved microRNA, which has been implicated in a variety of human cancers, including gliomas, colorectal cancer, non-small cell lung cancer, and prostate cancer 41 - 44 . In kidneys, Liu et al showed that miR-452 was up-regulated in clear-cell renal-cell carcinoma where it may promote cell proliferation and invasion by targeting SOX7, contributing to a poor 5-year survival in renal cancer patients 45 . This observation was verified by Zhai et al , although miR-452 was suggested to target SMAD4/SMAD7 signaling 46 .…”

Section: Discussionmentioning

confidence: 99%

Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis

Liu¹,

Yang²,

Gao³

et al. 2020

Theranostics

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Rationale: Sepsis is the cause of nearly half of acute kidney injury (AKI) and, unfortunately, AKI in sepsis is associated with unacceptably high rates of mortality. Early detection of AKI would guide the timely intervention and care of sepsis patients. Currently, NephroCheck, based on urinary [TIMP2]*[IGFBP7], is the only FDA approved test for early detection of AKI, which has a relatively low sensitivity for sepsis patients. Methods: In vitro , BUMPT (Boston University mouse proximal tubular cell line) cells were treated with lipopolysaccharides (LPS). In vivo , sepsis was induced in mice by LPS injection or cecal ligation and puncture (CLP). To validate the biomarker potential of miR-452, serum and urinary samples were collected from 47 sepsis patients with AKI, 50 patients without AKI, and 10 healthy subjects. Results: miR-452 was induced in renal tubular cells in septic AKI, and the induction was shown to be mediated by NF-κB. Notably, serum and urinary miR-452 increased early in septic mice following LPS or CLP treatment, prior to detectable renal dysfunction or tissue damage. Sepsis patients with AKI had significantly higher levels of serum and urinary miR-452 than the patients without AKI. Spearman's test demonstrated a remarkable positive correlation between urinary miR-452 and serum creatinine in sepsis patients (r=0.8269). The area under the receiver operating characteristic curve (AUC) was 0.8985 for urinary miR-452. Logistic regression analysis showed a striking 72.48-fold increase of AKI risk for every 1-fold increase of urinary miR-452 in sepsis patients. The sensitivity of urinary miR-452 for AKI detection in sepsis patients reached 87.23%, which was notably higher than the 61.54% achieved by urinary [TIMP2]*[IGFBP7], while the specificity of urinary miR-452 (78.00%) was slightly lower than that of [TIMP2]*[IGFBP7] (87.18%). Conclusions: miR-452 is induced via NF-κB in renal tubular cells in septic AKI. The increase of miR-452, especially that in urine, may be an effective biomarker for early detection of AKI in sepsis patients.

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“…Among all these key DEMs, miR-21 ( Fritz et al, 2014 ), miR-34a ( Fritz et al, 2015 ), miR-124 ( Butz et al, 2015 ), miR-141 ( Liep et al, 2016 ), miR-146a ( Yang et al, 2018 ), miR-155 ( Zhang et al, 2018 ), miR-200c ( Jiang et al, 2016 ), miR-210 ( Samaan et al, 2015 ), miR-224 ( Fujii et al, 2017 ), miR-452 ( Liu et al, 2018 ) and miR-142 ( Liu et al, 2010 ) have been reported to be correlated with ccRCC. Therefore, our findings are consistent with those from former studies.…”

Section: Discussionmentioning

confidence: 99%

Identification of the miRNA-mRNA regulatory pathways and a miR-21-5p based nomogram model in clear cell renal cell carcinoma

Zhao

Tao

Chen

2020

PeerJ

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Background The purpose of this study was to determine the key microRNAs (miRNAs) and their regulatory networks in clear cell renal cell carcinoma (ccRCC). Methods Five mRNA and three microRNA microarray datasets were downloaded from the Gene Expression Omnibus database and used to screen the differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs). Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed with Metascape. A miRNA-mRNA network was mapped with the Cytoscape tool. The results were validated with data from The Cancer Genome Atlas (TCGA) and qRT-PCR. A nomogram model based on independent prognostic key DEMs, stage and grade was constructed for further investigation. Results A total of 26 key DEMs and 307 DEGs were identified. Dysregulation of four key DEMs (miR-21-5p, miR-142-3p, miR-155-5p and miR-342-5p) was identified to correlate with overall survival. The results were validated with TCGA data and qRT-PCR. The nomogram model showed high accuracy in predicting the prognosis of patients with ccRCC. Conclusion We identified 26 DEMs that may play vital roles in the regulatory networks of ccRCC. Four miRNAs (miR-21-5p, miR-142-3p, miR-155-5p and miR-342-5p) were considered as potential biomarkers in the prognosis of ccRCC, among which only miR-21-5p was found to be an independent prognostic factor. A nomogram model was then created on the basis of independent factors for better prediction of prognosis for patients with ccRCC. Our results suggest a need for further experimental validation studies.

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miR‐452 promotes cell metastasis and the epithelial to mesenchymal by targeting SOX7 in clear‐cell renal‐cell carcinoma

Cited by 5 publications

References 40 publications

The transcription factor Sox7 modulates endocardiac cushion formation contributed to atrioventricular septal defect through Wnt4/Bmp2 signaling

The transcription factor Sox7 modulates endocardiac cushion formation contributed to atrioventricular septal defect through Wnt4/Bmp2 signaling

Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis

Identification of the miRNA-mRNA regulatory pathways and a miR-21-5p based nomogram model in clear cell renal cell carcinoma

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