Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway
Abstract Background Glioblastoma (GBM) is the most aggressive brain tumor. Reportedly, circular RNAs (circRNAs) participate in regulation of the development and progression of diverse cancers, including GBM. Methods Dysregulated circRNAs in GBM tissues were screened out from GEO database. The expres...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51743 |
| _version_ | 1797803320455200768 |
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| author | Yuhui Li Xuan Zheng Jiangong Wang Mingyang Sun Dan Li Zhuo Wang Jingwu Li Yufeng Li Yongliang Liu |
| author_facet | Yuhui Li Xuan Zheng Jiangong Wang Mingyang Sun Dan Li Zhuo Wang Jingwu Li Yufeng Li Yongliang Liu |
| author_sort | Yuhui Li |
| collection | DOAJ |
| description | Abstract Background Glioblastoma (GBM) is the most aggressive brain tumor. Reportedly, circular RNAs (circRNAs) participate in regulation of the development and progression of diverse cancers, including GBM. Methods Dysregulated circRNAs in GBM tissues were screened out from GEO database. The expression of candidate circRNAs in GBM cells was measured by qRT‐PCR. Loss‐of function assays, including colony formation assay, EdU assay, TUNEL assay, and flow cytometry analysis were conducted to determine the effects of circ‐AHCY knockdown on GBM cell proliferation and apoptosis. Animal study was further used to prove the inhibitory effect of circ‐AHCY silencing on GMB cell growth. Mechanistic experiments like luciferase reporter, RNA pull‐down and RNA‐binding protein immunoprecipitation (RIP) assays were performed to unveil the downstream molecular mechanism of circ‐AHCY. Nanosight Nanoparticle Tracking Analysis (NTA) and PKH67 staining were applied to identify the existence of exosomes. Results Circ‐AHCY was confirmed to be highly expressed in GBM cells. Circ‐AHCY silencing suppressed GBM cell proliferation both in vitro and in vivo. Mechanistically, circ‐AHCY activates Wnt/β‐catenin signaling pathway by sequestering miR‐1294 to up‐regulate MYC which activated CTNNB1 transcription. It was also found that circ‐AHCY recruited EIF4A3 to stabilize TCF4 mRNA. Enhanced levels of TCF4 and β‐catenin contributed to the stability of TCF4/β‐catenin complex. In turn, TCF4/β‐catenin complex strengthened the transcriptional activity of circ‐AHCY. Exosomal circ‐AHCY derived from GBM cells induced abnormal proliferation of normal human astrocytes (NHAs). Conclusion Exosomal circ‐AHCY forms a positive feedback loop with Wnt/β‐catenin signaling pathway to promote GBM cell growth. |
| first_indexed | 2024-03-13T05:19:02Z |
| format | Article |
| id | doaj.art-4f1253a415d346618e3803e27fa0fb9c |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-03-13T05:19:02Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-4f1253a415d346618e3803e27fa0fb9c2023-06-15T16:11:55ZengWileyAnnals of Clinical and Translational Neurology2328-95032023-06-0110686587810.1002/acn3.51743Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathwayYuhui Li0Xuan Zheng1Jiangong Wang2Mingyang Sun3Dan Li4Zhuo Wang5Jingwu Li6Yufeng Li7Yongliang Liu8Department of Neurosurgery Tangshan People's Hospital Tangshan Hebei 063001 ChinaThe Cancer Institute Tangshan People's Hospital Tangshan Hebei 063001 ChinaDepartment of Chemoradiotherapy Tangshan People's Hospital Tangshan Hebei 063001 ChinaDepartment of Neurosurgery Tangshan People's Hospital Tangshan Hebei 063001 ChinaThe Cancer Institute Tangshan People's Hospital Tangshan Hebei 063001 ChinaThe Cancer Institute Tangshan People's Hospital Tangshan Hebei 063001 ChinaThe Cancer Institute Tangshan People's Hospital Tangshan Hebei 063001 ChinaThe Cancer Institute Tangshan People's Hospital Tangshan Hebei 063001 ChinaDepartment of Neurosurgery Tangshan People's Hospital Tangshan Hebei 063001 ChinaAbstract Background Glioblastoma (GBM) is the most aggressive brain tumor. Reportedly, circular RNAs (circRNAs) participate in regulation of the development and progression of diverse cancers, including GBM. Methods Dysregulated circRNAs in GBM tissues were screened out from GEO database. The expression of candidate circRNAs in GBM cells was measured by qRT‐PCR. Loss‐of function assays, including colony formation assay, EdU assay, TUNEL assay, and flow cytometry analysis were conducted to determine the effects of circ‐AHCY knockdown on GBM cell proliferation and apoptosis. Animal study was further used to prove the inhibitory effect of circ‐AHCY silencing on GMB cell growth. Mechanistic experiments like luciferase reporter, RNA pull‐down and RNA‐binding protein immunoprecipitation (RIP) assays were performed to unveil the downstream molecular mechanism of circ‐AHCY. Nanosight Nanoparticle Tracking Analysis (NTA) and PKH67 staining were applied to identify the existence of exosomes. Results Circ‐AHCY was confirmed to be highly expressed in GBM cells. Circ‐AHCY silencing suppressed GBM cell proliferation both in vitro and in vivo. Mechanistically, circ‐AHCY activates Wnt/β‐catenin signaling pathway by sequestering miR‐1294 to up‐regulate MYC which activated CTNNB1 transcription. It was also found that circ‐AHCY recruited EIF4A3 to stabilize TCF4 mRNA. Enhanced levels of TCF4 and β‐catenin contributed to the stability of TCF4/β‐catenin complex. In turn, TCF4/β‐catenin complex strengthened the transcriptional activity of circ‐AHCY. Exosomal circ‐AHCY derived from GBM cells induced abnormal proliferation of normal human astrocytes (NHAs). Conclusion Exosomal circ‐AHCY forms a positive feedback loop with Wnt/β‐catenin signaling pathway to promote GBM cell growth.https://doi.org/10.1002/acn3.51743 |
| spellingShingle | Yuhui Li Xuan Zheng Jiangong Wang Mingyang Sun Dan Li Zhuo Wang Jingwu Li Yufeng Li Yongliang Liu Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway Annals of Clinical and Translational Neurology |
| title | Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway |
| title_full | Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway |
| title_fullStr | Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway |
| title_full_unstemmed | Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway |
| title_short | Exosomal circ‐AHCY promotes glioblastoma cell growth via Wnt/β‐catenin signaling pathway |
| title_sort | exosomal circ ahcy promotes glioblastoma cell growth via wnt β catenin signaling pathway |
| url | https://doi.org/10.1002/acn3.51743 |
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