GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A

Hui Yang; Xiaocen Liu; Xiaolong Zhu; Mengying Zhang; Yingying Wang; Mingzhe Ma; Kun Lv

doi:10.1016/j.isci.2022.104952

GINS1 promotes the proliferation and migration of glioma cells through USP15-mediated deubiquitination of TOP2A

iScience. 2022 Aug 17;25(9):104952. doi: 10.1016/j.isci.2022.104952. eCollection 2022 Sep 16.

Authors

Hui Yang^{1

2

3

4}, Xiaocen Liu^{2

3

5}, Xiaolong Zhu^{1

2

3}, Mengying Zhang^{1

2

3}, Yingying Wang⁵, Mingzhe Ma^{6

7}, Kun Lv^{1

2

3

4}

Affiliations

¹ Department of Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241001, China.
² Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes, Wannan Medical College, Wuhu 241001, China.
³ Non-coding RNA Research Center of Wannan Medical College, Wuhu 241001, China.
⁴ Anhui Province Clinical Research Center for Critical Respiratory Medicine, Wuhu 241001, China.
⁵ Department of Nuclear Medicine, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu 241001, China.
⁶ Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁷ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

Abstract

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.

Keywords: Biological sciences; Cancer; Cell biology; Molecular biology.