RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux
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 presen...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.887294/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Haiping Jiang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T03:04:15Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T03:04:15Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-cdaf20e0fe514efdb76d1cf07033be7f2022-12-22T00:40:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.887294887294RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic FluxHaiping Jiang0Haiping Jiang1Haiping Jiang2Dongzhi Zhang3Dongzhi Zhang4Dongzhi Zhang5Dongzhi Zhang6Karpov Denis Aleksandrovich7Karpov Denis Aleksandrovich8Karpov Denis Aleksandrovich9Karpov Denis Aleksandrovich10Junyi Ye11Junyi Ye12Junyi Ye13Lixiang Wang14Lixiang Wang15Lixiang Wang16Xiaofeng Chen17Xiaofeng Chen18Xiaofeng Chen19Ming Gao20Ming Gao21Ming Gao22Xinzhuang Wang23Xinzhuang Wang24Xinzhuang Wang25Tao Yan26Tao Yan27Tao Yan28He Yang29He Yang30He Yang31Enzhou Lu32Enzhou Lu33Enzhou Lu34Wenwu Liu35Wenwu Liu36Wenwu Liu37Cheng Zhang38Jianing Wu39Penglei Yao40Zhenying Sun41Xuan Rong42Sokhatskii Andrei Timofeevich43Sokhatskii Andrei Timofeevich44Sokhatskii Andrei Timofeevich45Sokhatskii Andrei Timofeevich46Safin Shamil Mahmutovich47Zhixing Zheng48Zhixing Zheng49Zhixing Zheng50Xin Chen51Xin Chen52Xin Chen53Shiguang Zhao54Shiguang Zhao55Shiguang Zhao56Shiguang Zhao57Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery and Medical Rehabilitation, Bashkir State Medical University, Ufa, RussiaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Undergraduate, Suffolk University, Boston, MA, United StatesDepartment of Neurosurgery, Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Neurosurgery, Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Neurosurgery, Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Neurosurgery, Shenzhen University General Hospital, Shenzhen, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery and Medical Rehabilitation, Bashkir State Medical University, Ufa, RussiaDepartment of Neurosurgery and Medical Rehabilitation, Bashkir State Medical University, Ufa, RussiaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Key Colleges and Universities Laboratory of Neurosurgery in Heilongjiang Province, Harbin, ChinaInstitute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Shenzhen University General Hospital, Shenzhen, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.887294/fullpectolinarigeninglioblastomaRRM2CDK1autophagic flux |
| spellingShingle | 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 RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux Frontiers in Oncology pectolinarigenin glioblastoma RRM2 CDK1 autophagic flux |
| title | RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux |
| title_full | RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux |
| title_fullStr | RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux |
| title_full_unstemmed | RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux |
| title_short | RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux |
| title_sort | rrm2 mediates the anti tumor effect of the natural product pectolinarigenin on glioblastoma through promoting cdk1 protein degradation by increasing autophagic flux |
| topic | pectolinarigenin glioblastoma RRM2 CDK1 autophagic flux |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.887294/full |
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