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Abnormal expression of menin predicts the pathogenesis and poor prognosis of adult gliomas

Cancer Gene Therapy volume 27, pages 539–547 (2020)Cite this article

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Abstract

Several brain tumors is closely related to the disorder of chromatin histone modification, whereas the epigenetic mechanisms of the incidence of highly malignant adult glioma is not yet deeply studied. Deletion or mutation of the MEN1 gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance of MEN1 in the nervous system remains poorly understood. Menin expression was robustly activated in 44.4% of adult gliomas. Abnormally high expression of menin was closely related to a shorter median survival time of 20 months, a larger tumor volume and a higher percentage of Ki67 staining. Interestingly, menin expression was also activated in the cytoplasm of tumor cells (38.8%) and was also closely related to the poor prognosis of patients with glioma. Importantly, in a screening of 96 types of small-molecule targeted histone modification regulators, menin inhibitors were found to significantly block the proliferation of adult glioma cells. Our findings confirm that menin is a potential biomarker of poor prognosis in adult gliomas, independent of the WHO grade. Targeting menin may effectively inhibit certain gliomas, and this information provides novel insight into therapeutic strategies for glioma.

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Acknowledgements

We appreciate the valuable comments by Dr. Shu-Bin Gao from our laboratory.

Funding

This study was supported by grants from the National Natural Science Foundation of China (U1605224, 81572778 to G.J., and 81872215, 81502444 to Q.Z.), and partly supported by Natural Science Foundation of Fujian Province (2019J01015 to Q.Z.), the Fundamental Research Funds for the Central Universities (20720190078 to Q.Z.), the Program for New Century Excellent Talents in University of Ministry of Education of China (NCET-10-0171 to Z.W.), the Technology Research Program of Jilin Province Health and Family Planning Commission (20152024 to Z.W.), the High Technology Research and Development Program of Jilin Province of China (2014G074 to Z.W.).

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Authors and Affiliations

  1. Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China

    Zhan-Feng Wang, Ming-Cheng Yuan & Xing-Li Zhao

  2. Department of Neurosurgery, the First Hospital of Jilin University, Changchun, Jilin, China

    Xin-Yu Hong

  3. Department of Basic Medical Sciences, School of Medicine, Xiamen, Fujian, China

    Ling-Yu Zhu, Li Zhang, Huan Qiu, Yuan-Yuan Zhang, Qi-Fan Zheng & Guang-Hui Jin

  4. State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China

    Guang-Hui Jin

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Wang, ZF., Hong, XY., Zhu, LY. et al. Abnormal expression of menin predicts the pathogenesis and poor prognosis of adult gliomas. Cancer Gene Ther 27, 539–547 (2020). https://doi.org/10.1038/s41417-019-0127-5

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