LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer
Abstract Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we furthe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04296-1 |
| _version_ | 1818981334050144256 |
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| author | Wenjie Luo Jun Wang Wenhao Xu Chunguang Ma Fangning Wan Yongqiang Huang Mengfei Yao Hailiang Zhang Yuanyuan Qu Dingwei Ye Yiping Zhu |
| author_facet | Wenjie Luo Jun Wang Wenhao Xu Chunguang Ma Fangning Wan Yongqiang Huang Mengfei Yao Hailiang Zhang Yuanyuan Qu Dingwei Ye Yiping Zhu |
| author_sort | Wenjie Luo |
| collection | DOAJ |
| description | Abstract Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer. |
| first_indexed | 2024-12-20T17:29:40Z |
| format | Article |
| id | doaj.art-5b785dd5f167465eab103a298882c1cb |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-20T17:29:40Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-5b785dd5f167465eab103a298882c1cb2022-12-21T19:31:25ZengNature Publishing GroupCell Death and Disease2041-48892021-11-01121111110.1038/s41419-021-04296-1LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancerWenjie Luo0Jun Wang1Wenhao Xu2Chunguang Ma3Fangning Wan4Yongqiang Huang5Mengfei Yao6Hailiang Zhang7Yuanyuan Qu8Dingwei Ye9Yiping Zhu10Department of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Sun Yat-sen University Cancer CenterDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Fudan University Shanghai Cancer CenterDepartment of Urology, Fudan University Shanghai Cancer CenterAbstract Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.https://doi.org/10.1038/s41419-021-04296-1 |
| spellingShingle | Wenjie Luo Jun Wang Wenhao Xu Chunguang Ma Fangning Wan Yongqiang Huang Mengfei Yao Hailiang Zhang Yuanyuan Qu Dingwei Ye Yiping Zhu LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer Cell Death and Disease |
| title | LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer |
| title_full | LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer |
| title_fullStr | LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer |
| title_full_unstemmed | LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer |
| title_short | LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer |
| title_sort | lncrna rp11 89 facilitates tumorigenesis and ferroptosis resistance through prom2 activated iron export by sponging mir 129 5p in bladder cancer |
| url | https://doi.org/10.1038/s41419-021-04296-1 |
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