RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma

Autor: Jiesi Zhou, Yan Shu Kong, Krista M. Vincent, Dylan Dieters‐Castator, Amirali B. Bukhari, Darryl Glubrecht, Rong‐Zong Liu, Douglas Quilty, Scott D. Findlay, Xiaowei Huang, Zhihua Xu, Rui Zhe Yang, Lanyue Zhang, Emily Tang, Gilles Lajoie, David D. Eisenstat, Armin M. Gamper, Richard Fahlman, Roseline Godbout, Lynne‐Marie Postovit, YangXin Fu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecular Oncology, Vol 17, Iss 9, Pp 1763-1783 (2023)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.13434
Popis: Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine‐C(5))‐methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM.
Databáze: Directory of Open Access Journals
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