Frontiers in Oncology (Apr 2022)
lncRNA PRADX is a Mesenchymal Glioblastoma Biomarker for Cellular Metabolism Targeted Therapy
- Can Xu,
- Can Xu,
- Jixing Zhao,
- Jixing Zhao,
- Jia Song,
- Jia Song,
- Menglin Xiao,
- Menglin Xiao,
- Xiaoteng Cui,
- Xiaoteng Cui,
- Lei Xin,
- Lei Xin,
- Jianglong Xu,
- Jianglong Xu,
- Yuhao Zhang,
- Yuhao Zhang,
- Kaikai Yi,
- Kaikai Yi,
- Biao Hong,
- Biao Hong,
- Fei Tong,
- Fei Tong,
- Shaohui Tian,
- Shaohui Tian,
- Yanli Tan,
- Yanli Tan,
- Chunsheng Kang,
- Chunsheng Kang,
- Chuan Fang,
- Chuan Fang
Affiliations
- Can Xu
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Can Xu
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Jixing Zhao
- Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China
- Jixing Zhao
- Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- Jia Song
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Jia Song
- School of Basic Medical Sciences, Hebei University, Baoding, China
- Menglin Xiao
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Menglin Xiao
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Xiaoteng Cui
- Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China
- Xiaoteng Cui
- Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- Lei Xin
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Lei Xin
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Jianglong Xu
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Jianglong Xu
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Yuhao Zhang
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Yuhao Zhang
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Kaikai Yi
- Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China
- Kaikai Yi
- Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- Biao Hong
- Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China
- Biao Hong
- Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- Fei Tong
- Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China
- Fei Tong
- Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- Shaohui Tian
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Shaohui Tian
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Yanli Tan
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- Yanli Tan
- School of Basic Medical Sciences, Hebei University, Baoding, China
- Chunsheng Kang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China
- Chunsheng Kang
- Key Laboratory of Post-Neurotrauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China
- Chuan Fang
- School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
- Chuan Fang
- Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China
- DOI
- https://doi.org/10.3389/fonc.2022.888922
- Journal volume & issue
-
Vol. 12
Abstract
Glioblastoma (GBM) is the most common and lethal type of primary malignant central nervous system (CNS) tumor with an extremely poor prognosis, and the mesenchymal subtype of GBM has the worst prognosis. Here, we found that lncRNA PRADX was overexpressed in the mesenchymal GBM and was transcriptionally regulated by RUNX1-CBFβ complex, overexpressed PRADX suppressed BLCAP expression via interacting with EZH2 and catalyzing trimethylation of lysine 27 on histone H3 (H3K27me3). Moreover, we showed that BLCAP interacted with STAT3 and reduced STAT3 phosphorylation, overexpressed PRADX activated STAT3 phosphorylation, and promoted ACSL1 expression via suppressing BLCAP expression, accelerating tumor metabolism. Finally, we determined that combined of ACSL1 and CPT1 inhibitors could reverse the accelerated cellular metabolism and tumor growth induced by PRADX overexpression in vivo and in vitro. Collectively, PRADX/PRC2 complex activated the STAT3 pathway and energy metabolism in relation to mesenchymal GBM progression. Furthermore, our findings provided a novel therapeutic strategy targeting the energy metabolism activity of GBM.
Keywords
