EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression
Abstract Emerging evidence indicates that circRNAs are broadly expressed in osteosarcoma (OS) cells and play a crucial role in OS progression. Recently, cancer-specific circRNA circPRKAR1B has been identified by high-throughput sequencing and is recorded in publicly available databases. Nevertheless...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04339-7 |
| _version_ | 1818690471811088384 |
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| author | Zhen-hua Feng Lin Zheng Teng Yao Si-yue Tao Xiao-an Wei Ze-yu Zheng Bing-jie Zheng Xu-yang Zhang Bao Huang Jun-hui Liu Yi-lei Chen Zhi Shan Pu-tao Yuan Cheng-gui Wang Jian Chen Shu-ying Shen Feng-dong Zhao |
| author_facet | Zhen-hua Feng Lin Zheng Teng Yao Si-yue Tao Xiao-an Wei Ze-yu Zheng Bing-jie Zheng Xu-yang Zhang Bao Huang Jun-hui Liu Yi-lei Chen Zhi Shan Pu-tao Yuan Cheng-gui Wang Jian Chen Shu-ying Shen Feng-dong Zhao |
| author_sort | Zhen-hua Feng |
| collection | DOAJ |
| description | Abstract Emerging evidence indicates that circRNAs are broadly expressed in osteosarcoma (OS) cells and play a crucial role in OS progression. Recently, cancer-specific circRNA circPRKAR1B has been identified by high-throughput sequencing and is recorded in publicly available databases. Nevertheless, the detailed functions and underlying mechanisms of circPRKAR1B in OS remains poorly understood. By functional experiments, we found that circPRKAR1B enhanced OS cell proliferation, migration, and promotes OS epithelial–mesenchymal transition (EMT). Mechanistic investigations suggested that circPRKAR1B promotes OS progression through sponging miR-361-3p to modulate the expression of FZD4. Subsequently, we identified that EIF4A3 promoted cirPRKAR1B formation through binding to the downstream target of circPRKAR1B on PRKAR1B mRNA. Further rescue study revealed that overexpression of the Wnt signalling could impair the onco-suppressor activities of the silencing of circPRKAR1B. Interestingly, further experiments indicated that circPRKAR1B is involved in the sensitivity of chemoresistance in OS. On the whole, our results demonstrated that circPRKAR1B exerted oncogenic roles in OS and suggested the circPRKAR1B/miR-361-3p/FZD4 axis plays an important role in OS progression and might be a potential therapeutic target. |
| first_indexed | 2024-12-17T12:26:32Z |
| format | Article |
| id | doaj.art-714b64b9eacc47b09f2264cc61071d92 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-17T12:26:32Z |
| publishDate | 2021-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-714b64b9eacc47b09f2264cc61071d922022-12-21T21:48:44ZengNature Publishing GroupCell Death and Disease2041-48892021-10-01121111410.1038/s41419-021-04339-7EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expressionZhen-hua Feng0Lin Zheng1Teng Yao2Si-yue Tao3Xiao-an Wei4Ze-yu Zheng5Bing-jie Zheng6Xu-yang Zhang7Bao Huang8Jun-hui Liu9Yi-lei Chen10Zhi Shan11Pu-tao Yuan12Cheng-gui Wang13Jian Chen14Shu-ying Shen15Feng-dong Zhao16Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineAbstract Emerging evidence indicates that circRNAs are broadly expressed in osteosarcoma (OS) cells and play a crucial role in OS progression. Recently, cancer-specific circRNA circPRKAR1B has been identified by high-throughput sequencing and is recorded in publicly available databases. Nevertheless, the detailed functions and underlying mechanisms of circPRKAR1B in OS remains poorly understood. By functional experiments, we found that circPRKAR1B enhanced OS cell proliferation, migration, and promotes OS epithelial–mesenchymal transition (EMT). Mechanistic investigations suggested that circPRKAR1B promotes OS progression through sponging miR-361-3p to modulate the expression of FZD4. Subsequently, we identified that EIF4A3 promoted cirPRKAR1B formation through binding to the downstream target of circPRKAR1B on PRKAR1B mRNA. Further rescue study revealed that overexpression of the Wnt signalling could impair the onco-suppressor activities of the silencing of circPRKAR1B. Interestingly, further experiments indicated that circPRKAR1B is involved in the sensitivity of chemoresistance in OS. On the whole, our results demonstrated that circPRKAR1B exerted oncogenic roles in OS and suggested the circPRKAR1B/miR-361-3p/FZD4 axis plays an important role in OS progression and might be a potential therapeutic target.https://doi.org/10.1038/s41419-021-04339-7 |
| spellingShingle | Zhen-hua Feng Lin Zheng Teng Yao Si-yue Tao Xiao-an Wei Ze-yu Zheng Bing-jie Zheng Xu-yang Zhang Bao Huang Jun-hui Liu Yi-lei Chen Zhi Shan Pu-tao Yuan Cheng-gui Wang Jian Chen Shu-ying Shen Feng-dong Zhao EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression Cell Death and Disease |
| title | EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression |
| title_full | EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression |
| title_fullStr | EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression |
| title_full_unstemmed | EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression |
| title_short | EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression |
| title_sort | eif4a3 induced circular rna prkar1b promotes osteosarcoma progression by mir 361 3p mediated induction of fzd4 expression |
| url | https://doi.org/10.1038/s41419-021-04339-7 |
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