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...

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Autores principales:	Wenjie Luo, Jun Wang, Wenhao Xu, Chunguang Ma, Fangning Wan, Yongqiang Huang, Mengfei Yao, Hailiang Zhang, Yuanyuan Qu, Dingwei Ye, Yiping Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/5b785dd5f167465eab103a298882c1cb
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spelling	oai:doaj.org-article:5b785dd5f167465eab103a298882c1cb2021-11-07T12:05:03ZLncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer10.1038/s41419-021-04296-12041-4889https://doaj.org/article/5b785dd5f167465eab103a298882c1cb2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04296-1https://doaj.org/toc/2041-4889Abstract 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.Wenjie LuoJun WangWenhao XuChunguang MaFangning WanYongqiang HuangMengfei YaoHailiang ZhangYuanyuan QuDingwei YeYiping ZhuNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 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
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.
format	article
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
title	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_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_sort	lncrna rp11-89 facilitates tumorigenesis and ferroptosis resistance through prom2-activated iron export by sponging mir-129-5p in bladder cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/5b785dd5f167465eab103a298882c1cb
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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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