Frontiers in Oncology (May 2022)
RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux
- Haiping Jiang,
- Haiping Jiang,
- Haiping Jiang,
- Dongzhi Zhang,
- Dongzhi Zhang,
- Dongzhi Zhang,
- Dongzhi Zhang,
- Karpov Denis Aleksandrovich,
- Karpov Denis Aleksandrovich,
- Karpov Denis Aleksandrovich,
- Karpov Denis Aleksandrovich,
- Junyi Ye,
- Junyi Ye,
- Junyi Ye,
- Lixiang Wang,
- Lixiang Wang,
- Lixiang Wang,
- Xiaofeng Chen,
- Xiaofeng Chen,
- Xiaofeng Chen,
- Ming Gao,
- Ming Gao,
- Ming Gao,
- Xinzhuang Wang,
- Xinzhuang Wang,
- Xinzhuang Wang,
- Tao Yan,
- Tao Yan,
- Tao Yan,
- He Yang,
- He Yang,
- He Yang,
- Enzhou Lu,
- Enzhou Lu,
- Enzhou Lu,
- Wenwu Liu,
- Wenwu Liu,
- Wenwu Liu,
- Cheng Zhang,
- Jianing Wu,
- Penglei Yao,
- Zhenying Sun,
- Xuan Rong,
- Sokhatskii Andrei Timofeevich,
- Sokhatskii Andrei Timofeevich,
- Sokhatskii Andrei Timofeevich,
- Sokhatskii Andrei Timofeevich,
- Safin Shamil Mahmutovich,
- Zhixing Zheng,
- Zhixing Zheng,
- Zhixing Zheng,
- Xin Chen,
- Xin Chen,
- Xin Chen,
- Shiguang Zhao,
- Shiguang Zhao,
- Shiguang Zhao,
- Shiguang Zhao
Affiliations
- Haiping Jiang
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Haiping Jiang
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Haiping Jiang
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Dongzhi Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Dongzhi Zhang
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Dongzhi Zhang
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Dongzhi Zhang
- Department of Neurosurgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, China
- Karpov Denis Aleksandrovich
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Karpov Denis Aleksandrovich
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Karpov Denis Aleksandrovich
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Karpov Denis Aleksandrovich
- Department of Neurosurgery and Medical Rehabilitation, Bashkir State Medical University, Ufa, Russia
- Junyi Ye
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Junyi Ye
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Junyi Ye
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Lixiang Wang
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Lixiang Wang
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Lixiang Wang
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Xiaofeng Chen
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Xiaofeng Chen
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Xiaofeng Chen
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Ming Gao
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Ming Gao
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Ming Gao
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Xinzhuang Wang
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Xinzhuang Wang
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Xinzhuang Wang
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Tao Yan
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Tao Yan
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Tao Yan
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- He Yang
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- He Yang
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- He Yang
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Enzhou Lu
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Enzhou Lu
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Enzhou Lu
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Wenwu Liu
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Wenwu Liu
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Wenwu Liu
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Cheng Zhang
- Department of Undergraduate, Suffolk University, Boston, MA, United States
- Jianing Wu
- Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China
- Penglei Yao
- Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China
- Zhenying Sun
- Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China
- Xuan Rong
- Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China
- Sokhatskii Andrei Timofeevich
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Sokhatskii Andrei Timofeevich
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Sokhatskii Andrei Timofeevich
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Sokhatskii Andrei Timofeevich
- Department of Neurosurgery and Medical Rehabilitation, Bashkir State Medical University, Ufa, Russia
- Safin Shamil Mahmutovich
- Department of Neurosurgery and Medical Rehabilitation, Bashkir State Medical University, Ufa, Russia
- Zhixing Zheng
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Zhixing Zheng
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Zhixing Zheng
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Xin Chen
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Xin Chen
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Xin Chen
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Shiguang Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
- Shiguang Zhao
- Department of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, China
- Shiguang Zhao
- Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China
- Shiguang Zhao
- Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, China
- DOI
- https://doi.org/10.3389/fonc.2022.887294
- Journal volume & issue
-
Vol. 12
Abstract
The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.
Keywords
