Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma

Author:

Chen Zigui,Yan Xin,Miao Changfeng,Liu Longyang,Liu Su,Xia Ying,Fang Weiyi,Zheng Dandan,Luo Qisheng

Abstract

AbstractMyosin heavy chain 9 (MYH9) plays an important role in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The present research aimed to investigate the role of MYH9 in glioma and determine whether MYH9 is involved in the temozolomide chemoresistance of glioma cells. Our results showed that MYH9 increased the proliferation and temozolomide resistance of glioma cells. The mechanistic experiments showed that the binding of MYH9 to NAP1L1, a potential promoter of tumor proliferation, inhibited the ubiquitination and degradation of NAP1L1 by recruiting USP14. Upregulation of NAP1L1 increased its binding with c-Myc and activated c-Myc, which induced the expression of CCND1/CDK4, promoting glioma cell temozolomide resistance and proliferation. Additionally, we found that MYH9 upregulation was strongly related to patient survival and is therefore a negative factor for patients with glioma. Altogether, our results show that MYH9 plays a role in glioma progression by regulating NAP1L1 deubiquitination. Thus, targeting MYH9 is a potential therapeutic strategy for the clinical treatment of glioma in the future.

Funder

President Foundation of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University

Haikou People’s Hospital to introduce high-level talent project in 2022

Natural Science Foundation of Guangxi Province

The First Batch of High-level Talent Scientific Research Projects of the Affiliated Hospital of Youjiang Medical University for Nationalities in 2019

Natural Science Foundation of Guangxi Zhuang Autonomous Region

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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