LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer.
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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LncRNA RP11-89 通过海绵 miR-129-5p 在膀胱癌中通过 PROM2 激活的铁输出促进肿瘤发生和铁死亡抵抗
DOI：
10.1038/s41419-021-04296-1
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发表时间：
2021-11-02
影响因子：
9
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Luo W;Wang J;Xu W;Ma C;Wan F;Huang Y;Yao M;Zhang H;Qu Y;Ye D;Zhu Y
长链非编码RNA（lncRNA）是膀胱癌发生发展的重要调控因子。然而，潜在的分子机制仍然难以捉摸。我们以前确定了一种新的lncRNA签名与免疫和膀胱癌的进展。在这里，我们进一步探索了RP 11 -89的功能，RP 11 -89是在之前的签名中发现的lncRNA。使用CCK-8测定、流式细胞术、Transwell测定、划痕试验和皮下裸鼠模型进行功能丧失和获得实验。进行高通量RNA测序以鉴定RP 11 -89敲低或过表达的膀胱癌细胞中的失调基因。通过荧光素酶报告基因分析、RIP分析和RNA pull-down分析探讨RP 11 -89对miR-129- 5 p和PROM 2的调控作用。RP 11 -89通过miR-129- 5 p/PROM 2轴促进细胞增殖、迁移和肿瘤发生，并抑制细胞周期阻滞。我们发现RP 11 -89“海绵”miR-129- 5 p并上调PROM 2。细胞中升高的PROM 2与通过铁输出减弱的铁凋亡、多泡体的形成和较少的线粒体异常相关。我们证明了RP 11 -89是一种新的致瘤调节因子，通过PROM 2激活的铁输出抑制铁凋亡。RP 11 -89可能作为膀胱癌靶向治疗的潜在生物标志物。
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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影响因子：
64.5
作者：
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