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LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes

Glioma is one of the most commonly diagnosed brain malignancies with a high cancer-related death rate in humans. The prognosis of glioma patients is still unsatisfactory. In the present study, we attempted to identify lncRNAs and miRNAs that might be related to NF-κB-mediated epithelial-mesenchymal...

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Autores principales: He, Zongze, Long, Juan, Yang, Chen, Gong, Bo, Cheng, Meixiong, Wang, Qi, Tang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655220/
https://www.ncbi.nlm.nih.gov/pubmed/33085646
http://dx.doi.org/10.18632/aging.103800
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author He, Zongze
Long, Juan
Yang, Chen
Gong, Bo
Cheng, Meixiong
Wang, Qi
Tang, Jian
author_facet He, Zongze
Long, Juan
Yang, Chen
Gong, Bo
Cheng, Meixiong
Wang, Qi
Tang, Jian
author_sort He, Zongze
collection PubMed
description Glioma is one of the most commonly diagnosed brain malignancies with a high cancer-related death rate in humans. The prognosis of glioma patients is still unsatisfactory. In the present study, we attempted to identify lncRNAs and miRNAs that might be related to NF-κB-mediated epithelial-mesenchymal transition in glioma cells based on online microarray expression profiles, and investigate the specific effects of lncRNA-miRNA-mRNA axes on glioma cell phenotypes. Herein, we identified lncRNA DGCR5 as a downregulated lncRNA in glioma that was negatively regulated by NF-κB1 in an NF-κB1 RE-dependent manner. LncRNA DGCR5 overexpression significantly inhibited the capacity of glioma cells to proliferate, migrate, and invade, whereas promoted the apoptosis of glioma cells. Moreover, lncRNA DGCR5 overexpression upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker VIM, as well as Snai2 and TWIST. Regarding the underlying molecular mechanisms, lncRNA DGCR5 could inhibit miR-21 and miR-23a expression, and miR-21 or miR-23a overexpression significantly reversed the tumor-suppressive effects of lncRNA DGCR5 overexpression. LncRNA DGCR5 exerted its tumor-suppressive effects through the DGCR5/miR-21/Smad7 and DGCR5/miR-23a/PTEN axes. In conclusion, lncRNA DGCR5 suppresses the capacity of glioma cells to migrate and invade via miR-21/Smad7, whereas it inhibits the proliferation and enhances the apoptosis of glioma cells through miR-23a/PTEN.
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spelling pubmed-76552202020-11-19 LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes He, Zongze Long, Juan Yang, Chen Gong, Bo Cheng, Meixiong Wang, Qi Tang, Jian Aging (Albany NY) Research Paper Glioma is one of the most commonly diagnosed brain malignancies with a high cancer-related death rate in humans. The prognosis of glioma patients is still unsatisfactory. In the present study, we attempted to identify lncRNAs and miRNAs that might be related to NF-κB-mediated epithelial-mesenchymal transition in glioma cells based on online microarray expression profiles, and investigate the specific effects of lncRNA-miRNA-mRNA axes on glioma cell phenotypes. Herein, we identified lncRNA DGCR5 as a downregulated lncRNA in glioma that was negatively regulated by NF-κB1 in an NF-κB1 RE-dependent manner. LncRNA DGCR5 overexpression significantly inhibited the capacity of glioma cells to proliferate, migrate, and invade, whereas promoted the apoptosis of glioma cells. Moreover, lncRNA DGCR5 overexpression upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker VIM, as well as Snai2 and TWIST. Regarding the underlying molecular mechanisms, lncRNA DGCR5 could inhibit miR-21 and miR-23a expression, and miR-21 or miR-23a overexpression significantly reversed the tumor-suppressive effects of lncRNA DGCR5 overexpression. LncRNA DGCR5 exerted its tumor-suppressive effects through the DGCR5/miR-21/Smad7 and DGCR5/miR-23a/PTEN axes. In conclusion, lncRNA DGCR5 suppresses the capacity of glioma cells to migrate and invade via miR-21/Smad7, whereas it inhibits the proliferation and enhances the apoptosis of glioma cells through miR-23a/PTEN. Impact Journals 2020-10-21 /pmc/articles/PMC7655220/ /pubmed/33085646 http://dx.doi.org/10.18632/aging.103800 Text en Copyright: © 2020 He et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
He, Zongze
Long, Juan
Yang, Chen
Gong, Bo
Cheng, Meixiong
Wang, Qi
Tang, Jian
LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes
title LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes
title_full LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes
title_fullStr LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes
title_full_unstemmed LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes
title_short LncRNA DGCR5 plays a tumor-suppressive role in glioma via the miR-21/Smad7 and miR-23a/PTEN axes
title_sort lncrna dgcr5 plays a tumor-suppressive role in glioma via the mir-21/smad7 and mir-23a/pten axes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655220/
https://www.ncbi.nlm.nih.gov/pubmed/33085646
http://dx.doi.org/10.18632/aging.103800
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