期刊
CELL DEATH & DISEASE
卷 12, 期 11, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41419-021-04296-1
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类别
资金
- National Natural Science Foundation of China [81772706, 81802525]
The lncRNA RP11-89 promotes cell proliferation, migration, tumorigenesis and inhibits cell cycle arrest through the miR-129-5p/PROM2 axis in bladder cancer. RP11-89 acts as a sponge for miR-129-5p, upregulating PROM2 and activating iron export, leading to attenuation of ferroptosis. RP11-89 is a novel tumorigenic regulator that may serve as a potential biomarker for targeted therapy in bladder cancer.
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.
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