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PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer

Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 (PUF60) as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics...

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Autores principales: Long, Qian, An, Xin, Chen, Miao, Wang, Nan, Sui, Silei, Li, Yixin, Zhang, Changlin, Lee, Kaping, Wang, Xiaonan, Tian, Tian, Pan, Yangxun, Qiu, Huijuan, Xie, Fangyun, Deng, Wuguo, Zheng, Fufu, He, Liru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576680/
https://www.ncbi.nlm.nih.gov/pubmed/33117697
http://dx.doi.org/10.3389/fonc.2020.568015
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author Long, Qian
An, Xin
Chen, Miao
Wang, Nan
Sui, Silei
Li, Yixin
Zhang, Changlin
Lee, Kaping
Wang, Xiaonan
Tian, Tian
Pan, Yangxun
Qiu, Huijuan
Xie, Fangyun
Deng, Wuguo
Zheng, Fufu
He, Liru
author_facet Long, Qian
An, Xin
Chen, Miao
Wang, Nan
Sui, Silei
Li, Yixin
Zhang, Changlin
Lee, Kaping
Wang, Xiaonan
Tian, Tian
Pan, Yangxun
Qiu, Huijuan
Xie, Fangyun
Deng, Wuguo
Zheng, Fufu
He, Liru
author_sort Long, Qian
collection PubMed
description Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 (PUF60) as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression of PUF60 was significantly higher in tumor tissues, while high PUF60 expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A (AURKA) as a new downstream target of PUF60 in bladder cancer cells. PUF60 knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas AURKA overexpression reversed this inhibition effect. Overexpression of PUF60 significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with AURKA specific inhibitor reversed this promotive effect. Mechanistically, PUF60 specifically bound to the AURKA promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between PUF60 and AURKA expression in bladder cancer tissues, and PUF60 and AURKA expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the PUF60/AURKA axis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients.
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spelling pubmed-75766802020-10-27 PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer Long, Qian An, Xin Chen, Miao Wang, Nan Sui, Silei Li, Yixin Zhang, Changlin Lee, Kaping Wang, Xiaonan Tian, Tian Pan, Yangxun Qiu, Huijuan Xie, Fangyun Deng, Wuguo Zheng, Fufu He, Liru Front Oncol Oncology Abnormal expression or mutation of RNA splicing proteins are widely observed in human cancers. Here, we identified poly(U) binding splicing factor 60 (PUF60) as one of the most differentially expressed genes out of 97 RNA splicing proteins between normal and bladder cancer tissues by bioinformatics analysis of TCGA bladder cancer expression data. The expression of PUF60 was significantly higher in tumor tissues, while high PUF60 expression was associated with malignant phenotypes of bladder cancer and shorter survival time. Moreover, we identified aurora kinase A (AURKA) as a new downstream target of PUF60 in bladder cancer cells. PUF60 knockdown significantly inhibited cell viability and colony formation capacity in bladder cancer cells, whereas AURKA overexpression reversed this inhibition effect. Overexpression of PUF60 significantly promoted cell viability and colony formation in bladder cancer cells, while treatment with AURKA specific inhibitor reversed this promotive effect. Mechanistically, PUF60 specifically bound to the AURKA promoter, thereby activating its transcription and expression. Furthermore, we showed that there was a significant positive correlation between PUF60 and AURKA expression in bladder cancer tissues, and PUF60 and AURKA expression contributed to tumor progression and malignant phenotypes in the patients with bladder cancer. Collectively, these results indicate that the PUF60/AURKA axis plays a key role in regulating tumorigenesis and progression of bladder cancer, and may be a potential prognostic biomarker and therapeutic target for bladder cancer patients. Frontiers Media S.A. 2020-10-07 /pmc/articles/PMC7576680/ /pubmed/33117697 http://dx.doi.org/10.3389/fonc.2020.568015 Text en Copyright © 2020 Long, An, Chen, Wang, Sui, Li, Zhang, Lee, Wang, Tian, Pan, Qiu, Xie, Deng, Zheng and He. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Long, Qian
An, Xin
Chen, Miao
Wang, Nan
Sui, Silei
Li, Yixin
Zhang, Changlin
Lee, Kaping
Wang, Xiaonan
Tian, Tian
Pan, Yangxun
Qiu, Huijuan
Xie, Fangyun
Deng, Wuguo
Zheng, Fufu
He, Liru
PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer
title PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer
title_full PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer
title_fullStr PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer
title_full_unstemmed PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer
title_short PUF60/AURKA Axis Contributes to Tumor Progression and Malignant Phenotypes in Bladder Cancer
title_sort puf60/aurka axis contributes to tumor progression and malignant phenotypes in bladder cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576680/
https://www.ncbi.nlm.nih.gov/pubmed/33117697
http://dx.doi.org/10.3389/fonc.2020.568015
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