LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer |
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| Authors: | Wenjie Luo Jun Wang Wenhao Xu Chunguang Ma Fangning Wan Yongqiang Huang Mengfei Yao Hailiang Zhang Yuanyuan Qu Dingwei Ye Yiping Zhu |
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| Affiliation: | 1.Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China ;2.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China ;3.Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China |
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| 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.Subject terms: Tumour biomarkers, Tumour biomarkers |
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