Cargando…

RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing

The prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progress...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Qiuxia, Zeng, Peng, Zhou, Xiuqin, Zhao, Xiaoying, Chen, Runqiang, Qiao, Jing, Feng, Ling, Zhu, Zhenjie, Zhang, Guozhi, Chen, Cairong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049873/
https://www.ncbi.nlm.nih.gov/pubmed/33564070
http://dx.doi.org/10.1038/s41388-021-01666-z
_version_ 1783679502359986176
author Yan, Qiuxia
Zeng, Peng
Zhou, Xiuqin
Zhao, Xiaoying
Chen, Runqiang
Qiao, Jing
Feng, Ling
Zhu, Zhenjie
Zhang, Guozhi
Chen, Cairong
author_facet Yan, Qiuxia
Zeng, Peng
Zhou, Xiuqin
Zhao, Xiaoying
Chen, Runqiang
Qiao, Jing
Feng, Ling
Zhu, Zhenjie
Zhang, Guozhi
Chen, Cairong
author_sort Yan, Qiuxia
collection PubMed
description The prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progression remains unclear. In this study, we found that RBMX was significantly downregulated in BCa tissues, especially in muscle-invasive BCa tissues. RBMX expression was negatively correlated with tumor stage, histological grade and poor patient prognosis. Functional assays demonstrated that RBMX inhibited BCa cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. Mechanistic investigations revealed that hnRNP A1 was an RBMX-binding protein. RBMX competitively inhibited the combination of the RGG motif in hnRNP A1 and the sequences flanking PKM exon 9, leading to the formation of lower PKM2 and higher PKM1 levels, which attenuated the tumorigenicity and progression of BCa. Moreover, RBMX inhibited aerobic glycolysis through hnRNP A1-dependent PKM alternative splicing and counteracted the PKM2 overexpression-induced aggressive phenotype of the BCa cells. In conclusion, our findings indicate that RBMX suppresses BCa tumorigenicity and progression via an hnRNP A1-mediated PKM alternative splicing mechanism. RBMX may serve as a novel prognostic biomarker for clinical intervention in BCa.
format Online
Article
Text
id pubmed-8049873
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-80498732021-04-29 RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing Yan, Qiuxia Zeng, Peng Zhou, Xiuqin Zhao, Xiaoying Chen, Runqiang Qiao, Jing Feng, Ling Zhu, Zhenjie Zhang, Guozhi Chen, Cairong Oncogene Article The prognosis for patients with metastatic bladder cancer (BCa) is poor, and it is not improved by current treatments. RNA-binding motif protein X-linked (RBMX) are involved in the regulation of the malignant progression of various tumors. However, the role of RBMX in BCa tumorigenicity and progression remains unclear. In this study, we found that RBMX was significantly downregulated in BCa tissues, especially in muscle-invasive BCa tissues. RBMX expression was negatively correlated with tumor stage, histological grade and poor patient prognosis. Functional assays demonstrated that RBMX inhibited BCa cell proliferation, colony formation, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo. Mechanistic investigations revealed that hnRNP A1 was an RBMX-binding protein. RBMX competitively inhibited the combination of the RGG motif in hnRNP A1 and the sequences flanking PKM exon 9, leading to the formation of lower PKM2 and higher PKM1 levels, which attenuated the tumorigenicity and progression of BCa. Moreover, RBMX inhibited aerobic glycolysis through hnRNP A1-dependent PKM alternative splicing and counteracted the PKM2 overexpression-induced aggressive phenotype of the BCa cells. In conclusion, our findings indicate that RBMX suppresses BCa tumorigenicity and progression via an hnRNP A1-mediated PKM alternative splicing mechanism. RBMX may serve as a novel prognostic biomarker for clinical intervention in BCa. Nature Publishing Group UK 2021-02-09 2021 /pmc/articles/PMC8049873/ /pubmed/33564070 http://dx.doi.org/10.1038/s41388-021-01666-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yan, Qiuxia
Zeng, Peng
Zhou, Xiuqin
Zhao, Xiaoying
Chen, Runqiang
Qiao, Jing
Feng, Ling
Zhu, Zhenjie
Zhang, Guozhi
Chen, Cairong
RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
title RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
title_full RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
title_fullStr RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
title_full_unstemmed RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
title_short RBMX suppresses tumorigenicity and progression of bladder cancer by interacting with the hnRNP A1 protein to regulate PKM alternative splicing
title_sort rbmx suppresses tumorigenicity and progression of bladder cancer by interacting with the hnrnp a1 protein to regulate pkm alternative splicing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049873/
https://www.ncbi.nlm.nih.gov/pubmed/33564070
http://dx.doi.org/10.1038/s41388-021-01666-z
work_keys_str_mv AT yanqiuxia rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT zengpeng rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT zhouxiuqin rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT zhaoxiaoying rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT chenrunqiang rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT qiaojing rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT fengling rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT zhuzhenjie rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT zhangguozhi rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing
AT chencairong rbmxsuppressestumorigenicityandprogressionofbladdercancerbyinteractingwiththehnrnpa1proteintoregulatepkmalternativesplicing