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MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53

Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined t...

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Autores principales: Zhou, Xu, Wu, Weining, Zeng, Ailiang, Nie, Er, Jin, Xin, Yu, Tianfu, Zhi, Tongle, Jiang, Kuan, Wang, Yingyi, Zhang, Junxia, You, Yongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642619/
https://www.ncbi.nlm.nih.gov/pubmed/29050344
http://dx.doi.org/10.18632/oncotarget.20528
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author Zhou, Xu
Wu, Weining
Zeng, Ailiang
Nie, Er
Jin, Xin
Yu, Tianfu
Zhi, Tongle
Jiang, Kuan
Wang, Yingyi
Zhang, Junxia
You, Yongping
author_facet Zhou, Xu
Wu, Weining
Zeng, Ailiang
Nie, Er
Jin, Xin
Yu, Tianfu
Zhi, Tongle
Jiang, Kuan
Wang, Yingyi
Zhang, Junxia
You, Yongping
author_sort Zhou, Xu
collection PubMed
description Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro. Bioinformatics analyses, luciferase reporter assays, and immunoblotting showed that p53 is a target gene of miR-141-3p. A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R(2)=0.506, P<0.0001). Rescue experiments indicated that overexpression of p53 significantly reversed the alterations in proliferation, cell cycle distribution, and temozolomide resistance measured by cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth of glioma cells in the brain and significantly prolonged the survival of glioma-bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and temozolomide resistance by altering p53 expression and therefore may serve as a new diagnostic marker and therapeutic target for glioma in the future.
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spelling pubmed-56426192017-10-18 MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53 Zhou, Xu Wu, Weining Zeng, Ailiang Nie, Er Jin, Xin Yu, Tianfu Zhi, Tongle Jiang, Kuan Wang, Yingyi Zhang, Junxia You, Yongping Oncotarget Research Paper Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro. Bioinformatics analyses, luciferase reporter assays, and immunoblotting showed that p53 is a target gene of miR-141-3p. A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R(2)=0.506, P<0.0001). Rescue experiments indicated that overexpression of p53 significantly reversed the alterations in proliferation, cell cycle distribution, and temozolomide resistance measured by cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth of glioma cells in the brain and significantly prolonged the survival of glioma-bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and temozolomide resistance by altering p53 expression and therefore may serve as a new diagnostic marker and therapeutic target for glioma in the future. Impact Journals LLC 2017-08-24 /pmc/articles/PMC5642619/ /pubmed/29050344 http://dx.doi.org/10.18632/oncotarget.20528 Text en Copyright: © 2017 Zhou et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 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
Zhou, Xu
Wu, Weining
Zeng, Ailiang
Nie, Er
Jin, Xin
Yu, Tianfu
Zhi, Tongle
Jiang, Kuan
Wang, Yingyi
Zhang, Junxia
You, Yongping
MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
title MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
title_full MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
title_fullStr MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
title_full_unstemmed MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
title_short MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
title_sort microrna-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642619/
https://www.ncbi.nlm.nih.gov/pubmed/29050344
http://dx.doi.org/10.18632/oncotarget.20528
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