Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR
Abstract Hypoxia is a common feature of glioblastoma (GBM). Circular RNAs (circRNAs) are identified as regulators in cancers. However, the role of circRNAs in GBM remains elusive. Here, circPLOD2a and circPLOD2b, spliced from the same parental gene PLOD2, are identified as hypoxia-responsive circRNA...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07503-3 |
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| author | Aixin Yu Yiqi Wang Chao Duan Jun Qin Miaomiao Liao Haiyan Zhu Junrong Lei Jun Liu Zehao Yang Li Yu Hui Gui Jinxin Xin Weiwei Tao Wendai Bao Zhiqiang Dong |
| author_facet | Aixin Yu Yiqi Wang Chao Duan Jun Qin Miaomiao Liao Haiyan Zhu Junrong Lei Jun Liu Zehao Yang Li Yu Hui Gui Jinxin Xin Weiwei Tao Wendai Bao Zhiqiang Dong |
| author_sort | Aixin Yu |
| collection | DOAJ |
| description | Abstract Hypoxia is a common feature of glioblastoma (GBM). Circular RNAs (circRNAs) are identified as regulators in cancers. However, the role of circRNAs in GBM remains elusive. Here, circPLOD2a and circPLOD2b, spliced from the same parental gene PLOD2, are identified as hypoxia-responsive circRNAs. Overexpression of circPLOD2a and b enhance while knockdown inhibit GBM cell aggressiveness. The protein partners and downstream molecules were investigated by RNA-pulldown, mass spectrometry and RNA-seq. Mechanistically, HIF1α induces the expression of circPLOD2a and b, which competitively bind to HuR, causing a degradation of XIRP1 in vitro and in vivo. Clinical data demonstrate circPLOD2a and b are highly expressed in GBM negatively correlated with XIRP1, whose lower expression associates with higher glioma grade and worse prognosis. In conclusion, hypoxia-induced circPLOD2a and b are oncogenic regulators of tumour aggressiveness through attenuating the interaction between HuR and XIRP1 in glioblastoma cells and may be potential therapeutic targets for this disease. |
| format | Article |
| id | doaj-art-16e10e29c3b44458bbd3dcf8772c59a8 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-16e10e29c3b44458bbd3dcf8772c59a82025-01-19T12:35:40ZengNature PortfolioCommunications Biology2399-36422025-01-018111510.1038/s42003-025-07503-3Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuRAixin Yu0Yiqi Wang1Chao Duan2Jun Qin3Miaomiao Liao4Haiyan Zhu5Junrong Lei6Jun Liu7Zehao Yang8Li Yu9Hui Gui10Jinxin Xin11Weiwei Tao12Wendai Bao13Zhiqiang Dong14Hubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineCollege of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural UniversityCollege of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural UniversityDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineCollege of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural UniversityHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineHubei Provincial Clinical Research Center of Central Nervous System Repair and Functional Reconstruction, Taihe Hospital, Hubei University of MedicineAbstract Hypoxia is a common feature of glioblastoma (GBM). Circular RNAs (circRNAs) are identified as regulators in cancers. However, the role of circRNAs in GBM remains elusive. Here, circPLOD2a and circPLOD2b, spliced from the same parental gene PLOD2, are identified as hypoxia-responsive circRNAs. Overexpression of circPLOD2a and b enhance while knockdown inhibit GBM cell aggressiveness. The protein partners and downstream molecules were investigated by RNA-pulldown, mass spectrometry and RNA-seq. Mechanistically, HIF1α induces the expression of circPLOD2a and b, which competitively bind to HuR, causing a degradation of XIRP1 in vitro and in vivo. Clinical data demonstrate circPLOD2a and b are highly expressed in GBM negatively correlated with XIRP1, whose lower expression associates with higher glioma grade and worse prognosis. In conclusion, hypoxia-induced circPLOD2a and b are oncogenic regulators of tumour aggressiveness through attenuating the interaction between HuR and XIRP1 in glioblastoma cells and may be potential therapeutic targets for this disease.https://doi.org/10.1038/s42003-025-07503-3 |
| spellingShingle | Aixin Yu Yiqi Wang Chao Duan Jun Qin Miaomiao Liao Haiyan Zhu Junrong Lei Jun Liu Zehao Yang Li Yu Hui Gui Jinxin Xin Weiwei Tao Wendai Bao Zhiqiang Dong Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR Communications Biology |
| title | Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR |
| title_full | Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR |
| title_fullStr | Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR |
| title_full_unstemmed | Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR |
| title_short | Hypoxia-induced circPLOD2a/b promotes the aggressiveness of glioblastoma by suppressing XIRP1 through binding to HuR |
| title_sort | hypoxia induced circplod2a b promotes the aggressiveness of glioblastoma by suppressing xirp1 through binding to hur |
| url | https://doi.org/10.1038/s42003-025-07503-3 |
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