Dr. Wangjia, from Prof. Wang Maode team, publishes a research article titled “Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2”, on Journal of Clinical Investigation (JCI, IF=12.574). JCI is established in 1924. The journal articles published on it are stressed on the combination of molecular biology and clinical medicine, and focused on basic research, translational medicine, early stage clinical study, and new research tools and technology. The magazine is medicine Class I periodical in both SCI and JCR section.

GBM is a kind of common intracrainial malignant tumor found in adult patients, the survival rate is below 5% in 5 years even subject to standard comprehensive treatment. According to the research findings, GSCs plays an important role in the generation, infiltration, and chemo resistance of GBM. Thus it’s of significance to clarify the molecular biological mechanisms of GSCs proliferation and differentiation in reducing recurrence of GBM and improving the clinical prognosis of GBM patients. The article explains that EZH2 post-interpretation regulatory mechanism participated by NEK2 is the key point in GBM recurrence and radiotherapy resistance for the first time.

EZH2, a member of PcG protein family, has been proved to show obvious high expression among various tumors, including glioma, and closely linked with poor prognosis, and plays an import role in proliferation and differentiation process of stem cells of various tumors. The transcription regulation of EZH2 on mRNA level is mainly subject to MELK and FOXM1, but the regulation of EZH2 on protein level remains unclear, which limits to a great extent the application prospect of taking EZH2 as targeted therapy of tumor. According to the new findings in this research, NEK2 may form protein complex after combining with EZH2 and improves the stability of EZH2 protein by interrupting the ubiquitination of GSCs in EZH2 through specific phosphorylation, which may further play its role in tumor proliferation and chemoresistance. In addition,a small-molecule inhibitor CMP3a is produced based on kinase activity of NEK2. It’s verified through in vivo and in vitro test that CMP3a may significantly decrease the proliferation infiltration of GSCs, and improve radiosensitivity of GSCs in cooperation with radiotherapy. Furthermore,it proves the application prospect of CMP3a in clinical treatment against GBM and provides a potential target spot and new idea for GBM treatment.

This research is completed by Dr. Wang Jia, from Neurosurgery Department of the First Affiliated Hospital of Xi’an Jiaotong University, under the guidance of Prof. Wang Maode and Prof. Ichiro Nakano from UAB after 3 years of efforts. Dr. Wang Jia is the first author of this article, Prof. Wang Maode is co-author, and the First Affiliated Hospital of Xi’an Jiaotong University is first organization and co-organization of the article. For the past few years, Prof. Wang Maode is committed to basic-clinical-transfer research of glioma and glioma stem cells and discipline construction. He focuses on the training of researcher’s clinical and scientific research thinking, and takes the training mode of engaging in clinical practice first and then basic research. Dr. Wang has obtained a number of achievements in scientific research with great clinical application prospect.