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TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner

BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain...

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Autores principales: Miao, Chenkui, Liang, Chao, Li, Pu, Liu, Bianjiang, Qin, Chao, Yuan, Han, Liu, Yiyang, Zhu, Jundong, Cui, Yankang, Xu, Aiming, Wang, Shangqian, Su, Shifeng, Li, Jie, Shao, Pengfei, Wang, Zengjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204444/
https://www.ncbi.nlm.nih.gov/pubmed/34130705
http://dx.doi.org/10.1186/s13046-021-01980-0
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author Miao, Chenkui
Liang, Chao
Li, Pu
Liu, Bianjiang
Qin, Chao
Yuan, Han
Liu, Yiyang
Zhu, Jundong
Cui, Yankang
Xu, Aiming
Wang, Shangqian
Su, Shifeng
Li, Jie
Shao, Pengfei
Wang, Zengjun
author_facet Miao, Chenkui
Liang, Chao
Li, Pu
Liu, Bianjiang
Qin, Chao
Yuan, Han
Liu, Yiyang
Zhu, Jundong
Cui, Yankang
Xu, Aiming
Wang, Shangqian
Su, Shifeng
Li, Jie
Shao, Pengfei
Wang, Zengjun
author_sort Miao, Chenkui
collection PubMed
description BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. METHODS: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. RESULTS: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01980-0.
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spelling pubmed-82044442021-06-16 TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner Miao, Chenkui Liang, Chao Li, Pu Liu, Bianjiang Qin, Chao Yuan, Han Liu, Yiyang Zhu, Jundong Cui, Yankang Xu, Aiming Wang, Shangqian Su, Shifeng Li, Jie Shao, Pengfei Wang, Zengjun J Exp Clin Cancer Res Research BACKGROUND: Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. METHODS: RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. RESULTS: We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. CONCLUSIONS: Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-021-01980-0. BioMed Central 2021-06-15 /pmc/articles/PMC8204444/ /pubmed/34130705 http://dx.doi.org/10.1186/s13046-021-01980-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Miao, Chenkui
Liang, Chao
Li, Pu
Liu, Bianjiang
Qin, Chao
Yuan, Han
Liu, Yiyang
Zhu, Jundong
Cui, Yankang
Xu, Aiming
Wang, Shangqian
Su, Shifeng
Li, Jie
Shao, Pengfei
Wang, Zengjun
TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
title TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
title_full TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
title_fullStr TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
title_full_unstemmed TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
title_short TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
title_sort trim37 orchestrates renal cell carcinoma progression via histone h2a ubiquitination-dependent manner
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204444/
https://www.ncbi.nlm.nih.gov/pubmed/34130705
http://dx.doi.org/10.1186/s13046-021-01980-0
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