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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Kidney Cancer | Research

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

Authors: Chenkui Miao, Chao Liang, Pu Li, Bianjiang Liu, Chao Qin, Han Yuan, Yiyang Liu, Jundong Zhu, Yankang Cui, Aiming Xu, Shangqian Wang, Shifeng Su, Jie Li, Pengfei Shao, Zengjun Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

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.

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Title: TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
Authors: Chenkui Miao
Chao Liang
Pu Li
Bianjiang Liu
Chao Qin
Han Yuan
Yiyang Liu
Jundong Zhu
Yankang Cui
Aiming Xu
Shangqian Wang
Shifeng Su
Jie Li
Pengfei Shao
Zengjun Wang
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Kidney Cancer
Kidney Cancer
Kidney Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01980-0

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Abstract

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