Cargando…

The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury

Background: Acute kidney injury (AKI) refers to a sudden loss of renal function. This study was performed to identify the key RNAs acting in the mechanism of sepsis-induced AKI. Methods: Microarray dataset GSE94717 (including six sepsis-induced AKI samples and three control samples) was downloaded f...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Guanhua, Mo, Lujiao, Wu, Channi, Shen, Xiaoyuan, Dong, Hongliang, Yu, Lingfeng, Pan, Ping, Pan, Kanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830252/
https://www.ncbi.nlm.nih.gov/pubmed/31658856
http://dx.doi.org/10.1080/0886022X.2019.1669460
_version_ 1783465744009265152
author Xu, Guanhua
Mo, Lujiao
Wu, Channi
Shen, Xiaoyuan
Dong, Hongliang
Yu, Lingfeng
Pan, Ping
Pan, Kanda
author_facet Xu, Guanhua
Mo, Lujiao
Wu, Channi
Shen, Xiaoyuan
Dong, Hongliang
Yu, Lingfeng
Pan, Ping
Pan, Kanda
author_sort Xu, Guanhua
collection PubMed
description Background: Acute kidney injury (AKI) refers to a sudden loss of renal function. This study was performed to identify the key RNAs acting in the mechanism of sepsis-induced AKI. Methods: Microarray dataset GSE94717 (including six sepsis-induced AKI samples and three control samples) was downloaded from Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were identified. The miRNA targets were predicted and enrichment analysis was performed. Protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) regulatory networks were constructed. Mouse podocytes were treated with lipopolysaccharide (LPS), following by cell viability and PCR analysis. Cellular apoptosis and the ceRNA network were validated. Results: Thirty-one common DE-miRNAs (two up-regulated and 29 down-regulated) by AKI versus control and male AKI versus control were identified. We found the targets of miR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway, and those of miR-29b-3p and miR-16-5p were enriched in PI3K-Akt signaling pathway. RNAs including miR-15b-5p, miR-15a-5p, miR-107, XIST, miR-16-5p, and cullin 3 gene (CUL3) were included in the ceRNA regulatory network. The downregulation of miR-15a-5p and miR-15b-5p and the upregulation of lncRNA XIST and CUL3 gene were validated using qPCR. The miR-15a-5p-XIST-CUL3 regulatory axis was identified and was validated. We confirmed that LPS inhibited the growth of mouse podocytes and seven of the ten miRNAs, but upregulated XIST and CUL3. Transfection analysis showed XIST siRNA enhanced LPS-induced MPC5 cell apoptosis and miR-15a-5p inhibitor reserved it, so did as CUL3 overexpression for miR-15a-5p mimics. Conclusion: The miR-15a-5p-XIST-CUL3 HIGHLIGHTS: Totally, 31 miRNAs were dysregulated between disease and control groups. MiR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway. MiR-16-5p and miR-29b-3p were implicated in PI3K-Akt signaling pathway. The miR-15a-5p-XIST-CUL3 axis was critical for sepsis-induced AKI.
format Online
Article
Text
id pubmed-6830252
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-68302522019-11-07 The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury Xu, Guanhua Mo, Lujiao Wu, Channi Shen, Xiaoyuan Dong, Hongliang Yu, Lingfeng Pan, Ping Pan, Kanda Ren Fail Laboratory Study Background: Acute kidney injury (AKI) refers to a sudden loss of renal function. This study was performed to identify the key RNAs acting in the mechanism of sepsis-induced AKI. Methods: Microarray dataset GSE94717 (including six sepsis-induced AKI samples and three control samples) was downloaded from Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were identified. The miRNA targets were predicted and enrichment analysis was performed. Protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) regulatory networks were constructed. Mouse podocytes were treated with lipopolysaccharide (LPS), following by cell viability and PCR analysis. Cellular apoptosis and the ceRNA network were validated. Results: Thirty-one common DE-miRNAs (two up-regulated and 29 down-regulated) by AKI versus control and male AKI versus control were identified. We found the targets of miR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway, and those of miR-29b-3p and miR-16-5p were enriched in PI3K-Akt signaling pathway. RNAs including miR-15b-5p, miR-15a-5p, miR-107, XIST, miR-16-5p, and cullin 3 gene (CUL3) were included in the ceRNA regulatory network. The downregulation of miR-15a-5p and miR-15b-5p and the upregulation of lncRNA XIST and CUL3 gene were validated using qPCR. The miR-15a-5p-XIST-CUL3 regulatory axis was identified and was validated. We confirmed that LPS inhibited the growth of mouse podocytes and seven of the ten miRNAs, but upregulated XIST and CUL3. Transfection analysis showed XIST siRNA enhanced LPS-induced MPC5 cell apoptosis and miR-15a-5p inhibitor reserved it, so did as CUL3 overexpression for miR-15a-5p mimics. Conclusion: The miR-15a-5p-XIST-CUL3 HIGHLIGHTS: Totally, 31 miRNAs were dysregulated between disease and control groups. MiR-15a-5p, miR-15b-5p, and miR-16-5p were involved in mTOR signaling pathway. MiR-16-5p and miR-29b-3p were implicated in PI3K-Akt signaling pathway. The miR-15a-5p-XIST-CUL3 axis was critical for sepsis-induced AKI. Taylor & Francis 2019-10-28 /pmc/articles/PMC6830252/ /pubmed/31658856 http://dx.doi.org/10.1080/0886022X.2019.1669460 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Laboratory Study
Xu, Guanhua
Mo, Lujiao
Wu, Channi
Shen, Xiaoyuan
Dong, Hongliang
Yu, Lingfeng
Pan, Ping
Pan, Kanda
The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury
title The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury
title_full The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury
title_fullStr The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury
title_full_unstemmed The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury
title_short The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury
title_sort mir-15a-5p-xist-cul3 regulatory axis is important for sepsis-induced acute kidney injury
topic Laboratory Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830252/
https://www.ncbi.nlm.nih.gov/pubmed/31658856
http://dx.doi.org/10.1080/0886022X.2019.1669460
work_keys_str_mv AT xuguanhua themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT molujiao themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT wuchanni themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT shenxiaoyuan themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT donghongliang themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT yulingfeng themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT panping themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT pankanda themir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT xuguanhua mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT molujiao mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT wuchanni mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT shenxiaoyuan mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT donghongliang mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT yulingfeng mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT panping mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury
AT pankanda mir15a5pxistcul3regulatoryaxisisimportantforsepsisinducedacutekidneyinjury