Oncotarget

Research Papers:

G protein-coupled receptor kinase 6 is overexpressed in glioma and promotes glioma cell proliferation

Li-Quan Xu, Shu-Bin Tan, Shan Huang, He-Yuan Ding, Wen-Gang Li, Yi Zhang, Shi-Qi Li and Tao Wang _

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Oncotarget. 2017; 8:54227-54235. https://doi.org/10.18632/oncotarget.17203

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Abstract

Li-Quan Xu1,*, Shu-Bin Tan1,*, Shan Huang1,*, He-Yuan Ding2, Wen-Gang Li1, Yi Zhang3, Shi-Qi Li3 and Tao Wang1

1Department of Neurosurgery, Shanghai 5th People’s Hospital, Shanghai Medical College, Fudan University, Shanghai, 200240, China

2Department of Endocrinology, Shanghai 5th People’s Hospital, Shanghai Medical College, Fudan University, Shanghai, 200240, China

3Department of Neurosurgery, HuaShan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China

*These authors contributed equally to this work

Correspondence to:

Tao Wang, email: [email protected]

Shi-Qi Li, email: [email protected]

Keywords: GRK6, glioma, proliferation, temozolomide

Received: March 10, 2017     Accepted: March 24, 2017     Published: April 18, 2017

ABSTRACT

The expression and potential biological functions of G protein-coupled receptor kinase 6 (GRK6) in human glioma are tested in this study. We show that protein and mRNA expression of GRK6 in human glioma tissues was significantly higher than that in the normal brain tissues. Further immunohistochemistry assay analyzing total 118 human glioma tissues showed that GRK6 over-expression was correlated with glioma pathologic grade and patients’ Karnofsky performance status (KPS) score. At the molecular level, in the GRK6-low H4 glioma cells, forced over-expression of GRK6 promoted cell proliferation. Reversely, siRNA-mediated knockdown of GRK6 in the U251MG (GRK6-high) cells led to proliferation inhibition and cell cycle arrest. Intriguingly, GRK6 could also be an important temozolomide resistance factor. Temozolomide-induced cytotoxicity was prominent only in GRK6-low H4 glioma cells. On the other hand, knockdown of GRK6 by targeted siRNA sensitized U251MG cells (GRK6-high) to temozolomide. Thus, GRK6 over-expression in glioma is important for cell proliferation and temozolomide resistance.


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