Journal article
NQO1-Mediated Oxidative Stress Resistance and Tumor Microenvironment Remodeling in Glioblastoma
Neuro-oncology (Charlottesville, Va.)
01/27/2026
DOI: 10.1093/neuonc/noag015
PMID: 41738493
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor, with glioblastoma stem cells (GSCs) occupying the pinnacle of a complex tumor microenvironment (TME), conferring therapeutic resistance. The TME plays a role in tumor development by creating a niche rich in reactive oxygen species (ROS) through oxidative stress (OS). Here, we identified NAD(P)H quinone oxidoreductase-1 (NQO1) as an essential regulatory factor in antioxidant stress response, which is key to maintaining GSCs and the immunosuppressive TME.
Proteomics analysis, epigenetic profile by using H3K27ac ChIP-sequencing and single-cell RNA sequencing were performed to define the high enrichment of NQO1 in GBM. In vitro and in vivo loss-of-function genetic and pharmacologic assays were conducted to evaluate the effect of NQO1 in GSC proliferation and self-renewal. Patient-derived GSCs and xenograft murine models were using to investigate the tumor-intrinsic and extrinsic mechanisms to confers resistance to oxidative stress and reprogram the immunosuppressive TME.
NQO1 was preferentially expressed in GSCs and regulated ROS levels, preserving the stability of nuclear Lamin B1 and inhibiting cGAS-type I interferon signaling, which helps to remodel the immunosuppressive TME. Furthermore, nuclear factor erythroid 2-related factor 2 (NRF2) transcriptionally regulates NQO1, suppressing type I interferon signaling.
NQO1 plays critical roles at both the cell-autonomous and cell-extrinsic levels for clinical treatment. Targeting NQO1 and its downstream signaling pathways, including β-Lapachone and immune checkpoint inhibitors such as anti-PD-1 therapy, enhances our understanding of the interactions between GSCs, oxidative stress, and the TME. This offers promising new avenues for clinical intervention in GBM.
Details
- Title: Subtitle
- NQO1-Mediated Oxidative Stress Resistance and Tumor Microenvironment Remodeling in Glioblastoma
- Creators
- Yangqing Li - Model Animal Research CenterTao Kang - Nanjing Medical UniversityZhen Jia - Nanjing Medical UniversityChenfei Lu - Nanjing Medical UniversityGaoyuan Cui - Nanjing Medical UniversityKefan Song - Nanjing Medical UniversityHang Yu - Nanjing Medical UniversityDeobrat Dixit - Columbia University Irving Medical CenterFangshu Jin - Second Affiliated Hospital of Nanjing Medical UniversityDanyang Shan - Nanjing Medical UniversityQiankun Lin - Nanjing Medical UniversityDaqi Li - Nanjing Medical UniversityHao You - Nanjing Medical UniversityDanling Gu - Nanjing Medical UniversityJiancheng Gao - Nanjing Medical UniversityZhumei Shi - Nanjing Medical UniversityWei Gao - Nanjing Medical UniversityFan Lin - Nanjing Medical UniversityZhe Zhu - Columbia University Irving Medical CenterQianghu Wang - Nanjing Medical UniversityWeiwei Tao - Huazhong Agricultural UniversityJunxia Zhang - Nanjing Medical UniversityJingshan Liang - The First People’s Hospital of LianyungangZhu Zhu - Columbia University Irving Medical CenterYongping You - Jiangsu Province HospitalXu Qian - Jiangsu Cancer HospitalKailin Yang - University of IowaXiuxing Wang - Nanjing Medical UniversityJeremy N Rich - University of North Carolina at Chapel HillKun Yang - Zhongda Hospital Southeast UniversityLuan Sun - Changzhou No.2 People's HospitalChaojun Li - Nanjing Health and Health CommissionQian Zhang - Jiangsu Cancer Hospital
- Resource Type
- Journal article
- Publication Details
- Neuro-oncology (Charlottesville, Va.)
- DOI
- 10.1093/neuonc/noag015
- PMID
- 41738493
- NLM abbreviation
- Neuro Oncol
- ISSN
- 1523-5866
- eISSN
- 1523-5866
- Publisher
- OXFORD UNIV PRESS INC
- Grant note
- Medical Science and Technology Development Foundation of Nanjing: ZKX22041 Clinical Research Foundation for the Prevention and Treatment of Collaborative Innovation Center for Cancer Personalized Medicine of Nanjing Medical University: 2024CICCPMHR036, 2024CICCPMHR015 Research Personnel Cultivation Programme of Zhongda Hospital Southeast University: CZXM-GSP-RC-152 Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds: zdlyg05 National Natural Science Foundation of China: 82573312, 82525047, 82403659 Natural Science Foundation of Jiangsu Province: BK20241130
This research was supported by the National Natural Science Foundation of China (grants 82573312 to Q.Z., 82525047 to X.W., and 82403659 to C.L.); the Clinical Research Foundation for the Prevention and Treatment of Collaborative Innovation Center for Cancer Personalized Medicine of Nanjing Medical University (grants 2024CICCPMHR036 to Q.Z. and 2024CICCPMHR015 to X.W.); the Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds (grant zdlyg05 to K.Y.); the Research Personnel Cultivation Programme of Zhongda Hospital Southeast University (grant CZXM-GSP-RC-152 to K.Y.), the Medical Science and Technology Development Foundation of Nanjing (grant ZKX22041 to K.Y.), and Natural Science Foundation of Jiangsu Province (grant BK20241130 to C.L.).
- Language
- English
- Electronic publication date
- 01/27/2026
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9985139310502771
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