Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and enhances temozolomide response in Glioma

Abstract Myosin heavy chain 9 (MYH9) has been significantly involved in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The article aims to investigate the effect of MYH9 and to determine if MYH9 is also implicated in temozolomide chemoresistance of glioma. Here, we first found that MYH9 increased cell proliferation and temozolomide resistance in glioma. Mechanistic studies showed that MYH9 bound to NAP1L1, a potential tumor promoter has been reported to promote the tumor proliferation, and further inhibited ubiquitination and degradation of NAP1L1 by recruiting USP14. The up-regulated NAP1L1 increased the binding with c-Myc and further activated c-Myc, which induce the expression of CCND1/CDK4, thereby promoting temozolomide resistance and cell proliferation in glioma. In addition, we found that up-regulated MYH9 level was strongly related to patient survival and should be demonstrated as a negative factor in patients with glioma. Taken together, our results offer a new perspective on the role of MYH9 in glioma progression by regulating NAP1L1 deubiquitination, targeting MYH9 will have the possible clinical application in glioma treatment going forward.