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

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.

• 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
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 40 Issue 1 Pg. 195 (Jun 15 2021) ISSN: 1756-9966 [Electronic] England
• PMID: 34130705 (Publication Type: Journal Article)

Chemical References

• Histones
• Tripartite Motif Proteins
• TRIM37 protein, human
• Ubiquitin-Protein Ligases

Topics

• Animals
• Carcinoma, Renal Cell (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Disease Progression
• Heterografts
• Histones (genetics, metabolism)
• Humans
• Kidney Neoplasms (genetics, metabolism)
• Male
• Mice
• Mice, Nude
• Middle Aged
• Signal Transduction
• Transfection
• Tripartite Motif Proteins (metabolism)
• Ubiquitin-Protein Ligases (metabolism)
• Ubiquitination