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Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3

Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an impor...

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Autores principales: Jia, Bo, Jiang, Yuran, Huan, Yu, Han, Yu, Liu, Wei, Liu, Xiao, Wang, Yingwen, He, Lei, Cao, Zhengcong, He, Xin, Zhang, Kuo, Gu, Jintao, Guo, Qingdong, Fei, Zhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458994/
https://www.ncbi.nlm.nih.gov/pubmed/37595394
http://dx.doi.org/10.1016/j.tranon.2023.101756
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author Jia, Bo
Jiang, Yuran
Huan, Yu
Han, Yu
Liu, Wei
Liu, Xiao
Wang, Yingwen
He, Lei
Cao, Zhengcong
He, Xin
Zhang, Kuo
Gu, Jintao
Guo, Qingdong
Fei, Zhou
author_facet Jia, Bo
Jiang, Yuran
Huan, Yu
Han, Yu
Liu, Wei
Liu, Xiao
Wang, Yingwen
He, Lei
Cao, Zhengcong
He, Xin
Zhang, Kuo
Gu, Jintao
Guo, Qingdong
Fei, Zhou
author_sort Jia, Bo
collection PubMed
description Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an important role in the malignant biological progression of a variety of tumors. However, the underlying role and mechanism in glioma remain poorly understood. By using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry and Orthotopic mouse xenografts, we confirmed that knockdown of RACGAP1 impeded cell proliferation in glioma and prolonged the survival of orthotopic mice. Interestingly, we also found that inhibiting the expression of RACGAP1 reduced the expression of minichromosome maintenance 3 (MCM3) through RNA-seq and rescue assay, while Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression. Furthermore, T7 peptide-decorated exosome (T7-exo) is regard as a promising delivery modality for targeted therapy of glioma, and the T7-siRACGAP1-exo significantly improved the survival time of glioma bearing mice. These results suggested that targeting RACGAP1 may be a potential strategy for glioma therapy.
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spelling pubmed-104589942023-08-27 Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3 Jia, Bo Jiang, Yuran Huan, Yu Han, Yu Liu, Wei Liu, Xiao Wang, Yingwen He, Lei Cao, Zhengcong He, Xin Zhang, Kuo Gu, Jintao Guo, Qingdong Fei, Zhou Transl Oncol Original Research Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an important role in the malignant biological progression of a variety of tumors. However, the underlying role and mechanism in glioma remain poorly understood. By using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry and Orthotopic mouse xenografts, we confirmed that knockdown of RACGAP1 impeded cell proliferation in glioma and prolonged the survival of orthotopic mice. Interestingly, we also found that inhibiting the expression of RACGAP1 reduced the expression of minichromosome maintenance 3 (MCM3) through RNA-seq and rescue assay, while Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression. Furthermore, T7 peptide-decorated exosome (T7-exo) is regard as a promising delivery modality for targeted therapy of glioma, and the T7-siRACGAP1-exo significantly improved the survival time of glioma bearing mice. These results suggested that targeting RACGAP1 may be a potential strategy for glioma therapy. Neoplasia Press 2023-08-16 /pmc/articles/PMC10458994/ /pubmed/37595394 http://dx.doi.org/10.1016/j.tranon.2023.101756 Text en © 2023 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Jia, Bo
Jiang, Yuran
Huan, Yu
Han, Yu
Liu, Wei
Liu, Xiao
Wang, Yingwen
He, Lei
Cao, Zhengcong
He, Xin
Zhang, Kuo
Gu, Jintao
Guo, Qingdong
Fei, Zhou
Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3
title Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3
title_full Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3
title_fullStr Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3
title_full_unstemmed Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3
title_short Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3
title_sort rac gtpase activating protein 1 promotes the glioma growth by regulating the expression of mcm3
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458994/
https://www.ncbi.nlm.nih.gov/pubmed/37595394
http://dx.doi.org/10.1016/j.tranon.2023.101756
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