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GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A
GINS1 is a GINS complex subunit that functions along with the MCM2-7 complex and Cdc45 in eukaryotic DNA replication. Despite the significance of the GINS complex in the switch between quiescence and proliferation of glioma cells inside and outside the perinecrotic niche, the biological functions an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440292/ https://www.ncbi.nlm.nih.gov/pubmed/36065190 http://dx.doi.org/10.1016/j.isci.2022.104952 |
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author | Yang, Hui Liu, Xiaocen Zhu, Xiaolong Zhang, Mengying Wang, Yingying Ma, Mingzhe Lv, Kun |
author_facet | Yang, Hui Liu, Xiaocen Zhu, Xiaolong Zhang, Mengying Wang, Yingying Ma, Mingzhe Lv, Kun |
author_sort | Yang, Hui |
collection | PubMed |
description | GINS1 is a GINS complex subunit that functions along with the MCM2-7 complex and Cdc45 in eukaryotic DNA replication. Despite the significance of the GINS complex in the switch between quiescence and proliferation of glioma cells inside and outside the perinecrotic niche, the biological functions and the underlying mechanism of GINS1 remain unclear. Unlike in normal cells and tissues, GINS1 expression level was significantly upregulated in glioma cells and tissues. High expression of GINS1 predicted an advanced clinical grade and a poor survival. Functional assays revealed that GINS1 aggravated glioma malignant phenotypes in vitro and in vivo. Mechanistically, this study identified that GINS1 physically interacts with TOP2A. GINS1 promotes glioma cell proliferation and migration through USP15-mediated deubiquitination of TOP2A protein. Our results delineate the clinical significance of GINS1 in glioma and the regulatory mechanisms involved in glioma cell proliferation and migration. This work provides potential therapeutic targets for glioma treatment. |
format | Online Article Text |
id | pubmed-9440292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-94402922022-09-04 GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A Yang, Hui Liu, Xiaocen Zhu, Xiaolong Zhang, Mengying Wang, Yingying Ma, Mingzhe Lv, Kun iScience Article GINS1 is a GINS complex subunit that functions along with the MCM2-7 complex and Cdc45 in eukaryotic DNA replication. Despite the significance of the GINS complex in the switch between quiescence and proliferation of glioma cells inside and outside the perinecrotic niche, the biological functions and the underlying mechanism of GINS1 remain unclear. Unlike in normal cells and tissues, GINS1 expression level was significantly upregulated in glioma cells and tissues. High expression of GINS1 predicted an advanced clinical grade and a poor survival. Functional assays revealed that GINS1 aggravated glioma malignant phenotypes in vitro and in vivo. Mechanistically, this study identified that GINS1 physically interacts with TOP2A. GINS1 promotes glioma cell proliferation and migration through USP15-mediated deubiquitination of TOP2A protein. Our results delineate the clinical significance of GINS1 in glioma and the regulatory mechanisms involved in glioma cell proliferation and migration. This work provides potential therapeutic targets for glioma treatment. Elsevier 2022-08-17 /pmc/articles/PMC9440292/ /pubmed/36065190 http://dx.doi.org/10.1016/j.isci.2022.104952 Text en © 2022 The Author(s) 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 | Article Yang, Hui Liu, Xiaocen Zhu, Xiaolong Zhang, Mengying Wang, Yingying Ma, Mingzhe Lv, Kun GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A |
title | GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A |
title_full | GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A |
title_fullStr | GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A |
title_full_unstemmed | GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A |
title_short | GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A |
title_sort | gins1 promotes the proliferation and migration of glioma cells through usp15-mediated deubiquitination of top2a |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9440292/ https://www.ncbi.nlm.nih.gov/pubmed/36065190 http://dx.doi.org/10.1016/j.isci.2022.104952 |
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