Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma
Abstract Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was up...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05056-5 |
| _version_ | 1811293852213968896 |
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| author | Xiuchao Geng Yuhao Zhang Xiaomeng Lin Zhaomu Zeng Jun Hu Liangchao Hao Jianglong Xu Xinjuan Wang Hong Wang Qiang Li |
| author_facet | Xiuchao Geng Yuhao Zhang Xiaomeng Lin Zhaomu Zeng Jun Hu Liangchao Hao Jianglong Xu Xinjuan Wang Hong Wang Qiang Li |
| author_sort | Xiuchao Geng |
| collection | DOAJ |
| description | Abstract Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was upregulated in TMZ-resistant glioma cells and TMZ-resistant glioma cell-derived exosomes compared with their controls by using high-throughput microarray analysis and quantitative real-time polymerase chain reaction, and high circWDR62 expression was associated with poor prognosis of glioma. Functionally, downregulation of circWDR62 expression could significantly inhibit the TMZ resistance and malignant progression of glioma. Further mechanistic studies showed that circWDR62 plays a role by sponging miR-370-3p as a competing endogenous RNA. Rescue experiments confirmed that MGMT is the downstream target of the circWDR62/miR-370-3p axis in glioma. In addition, circWDR62 could be transported between TMZ-resistant and TMZ-sensitive glioma cells via exosomes. Exosomal circWDR62 from TMZ-resistant cells conferred TMZ resistance in recipient sensitive cells while also enhancing the proliferation, migration and invasion of these cells. A series of clinical and in vivo trials corroborated that exosomal circWDR62 could promote TMZ chemoresistance and malignant progression of glioma. Our results demonstrate for the first time that exosome-mediated delivery of circWDR62 can promote TMZ resistance and malignant progression via targeting of the miR-370-3p/MGMT axis in vitro and in vivo in glioma, providing a new therapeutic strategy. Moreover, exosomal circWDR62 in human serum may serve as a promising therapeutic target and prognostic marker for glioma therapy. |
| first_indexed | 2024-04-13T05:07:41Z |
| format | Article |
| id | doaj.art-e3d00c0a71ac429e977bbc17b1a10625 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T05:07:41Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-e3d00c0a71ac429e977bbc17b1a106252022-12-22T03:01:07ZengNature Publishing GroupCell Death and Disease2041-48892022-07-0113711510.1038/s41419-022-05056-5Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in gliomaXiuchao Geng0Yuhao Zhang1Xiaomeng Lin2Zhaomu Zeng3Jun Hu4Liangchao Hao5Jianglong Xu6Xinjuan Wang7Hong Wang8Qiang Li9Taizhou Central Hosiptal (Taizhou University Hospital), Taizhou UniversityDepartment of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated to Hangzhou Medical CollegeDepartments of Breast Surgery, Affiliated Hospital of Hebei UniversityDepartment of Neurosurgery, Affiliated Hospital of Hebei UniversityFaculty of Integrated Traditional Chinese and Western Medicine, Hebei University of Chinese MedicineDepartment of Plastic Surgery, Shaoxing People’s HospitalKey Laboratory of Precise Diagnosis and Treatment of Glioma in Hebei ProvienceSchool of Medicine, Taizhou UniversityDepartment of Neurosurgery, Affiliated Hospital of Hebei UniversitySchool of Medicine, Taizhou UniversityAbstract Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was upregulated in TMZ-resistant glioma cells and TMZ-resistant glioma cell-derived exosomes compared with their controls by using high-throughput microarray analysis and quantitative real-time polymerase chain reaction, and high circWDR62 expression was associated with poor prognosis of glioma. Functionally, downregulation of circWDR62 expression could significantly inhibit the TMZ resistance and malignant progression of glioma. Further mechanistic studies showed that circWDR62 plays a role by sponging miR-370-3p as a competing endogenous RNA. Rescue experiments confirmed that MGMT is the downstream target of the circWDR62/miR-370-3p axis in glioma. In addition, circWDR62 could be transported between TMZ-resistant and TMZ-sensitive glioma cells via exosomes. Exosomal circWDR62 from TMZ-resistant cells conferred TMZ resistance in recipient sensitive cells while also enhancing the proliferation, migration and invasion of these cells. A series of clinical and in vivo trials corroborated that exosomal circWDR62 could promote TMZ chemoresistance and malignant progression of glioma. Our results demonstrate for the first time that exosome-mediated delivery of circWDR62 can promote TMZ resistance and malignant progression via targeting of the miR-370-3p/MGMT axis in vitro and in vivo in glioma, providing a new therapeutic strategy. Moreover, exosomal circWDR62 in human serum may serve as a promising therapeutic target and prognostic marker for glioma therapy.https://doi.org/10.1038/s41419-022-05056-5 |
| spellingShingle | Xiuchao Geng Yuhao Zhang Xiaomeng Lin Zhaomu Zeng Jun Hu Liangchao Hao Jianglong Xu Xinjuan Wang Hong Wang Qiang Li Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma Cell Death and Disease |
| title | Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma |
| title_full | Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma |
| title_fullStr | Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma |
| title_full_unstemmed | Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma |
| title_short | Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma |
| title_sort | exosomal circwdr62 promotes temozolomide resistance and malignant progression through regulation of the mir 370 3p mgmt axis in glioma |
| url | https://doi.org/10.1038/s41419-022-05056-5 |
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