title: Birth of MTH1 as a therapeutic target for glioblastoma: MTH1 is indispensable for gliomatumorigenesis.
abstract: Malignant glioma is the most common primary tumor of the central nervous system. Chemotherapy and radiotherapy are the most common therapeutic approaches in glioma therapy. Both processes mainly kill cancer cells through generating high Reactive Oxygen Species (ROS) and lead to oxidative DNA damage. However, tumor resistance to ROS is always a challenge for cancer treatment. Human Mut T homolog 1 (MTH1, also known as NUDT1) is regarded as a protector of nucleotides against oxidization. Recent reports have verified that overexpression of MTH1 could remove oxidized dNTP pools. Here, we find that MTH1 is overexpressed both at mRNA and protein levels in GBM. MTH1 silencing inhibits colony formation; tumor spheres formation and xenograft tumor growth, and more importantly, the viability of glioma cells is significantly decreased in H2O2 after MTH1 was knocked down in glioma. PI staining show that H2O2 cause more glioma cell death after MTH1 silencing. So we speculate that overexpression of MTH1 is crucial for glioma survival, suppression of its expression can inhibit cancer cell survival in vitro and in vivo, MTH1 may be a potential target for human glioma therapy in future.
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical UniversityXi'an 710038, China; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical SchoolBoston, MA, 02115, USA.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University Xi'an 710038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School Boston, MA, 02115, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School Boston, MA, 02115, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University Xi'an 710038, China.
authors.forename: Pengxing
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School Boston, MA, 02115, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University Xi'an 710038, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University Xi'an 710038, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University Xi'an 710038, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University Shanghai 200240, China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
keywords: GBM; MTH1; reactive oxygen species; stemness; viability