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RNF168 promotes RHOC degradation by ubiquitination to restrain gastric cancer progression via decreasing HDAC1 expression
- Source :
- Biochemical and Biophysical Research Communications. 557:135-142
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Gastric cancer (GC) is the most common cancer worldwide. Although advances in the treatments, the oncogenic mechanisms are still largely unknown. RNF168 (ring-finger nuclear factor 168) is an important regulator of DNA double-strand break (DSB) repair, and its defects have been involved in the pathogenesis of a number of human diseases including cancer. However, its effects on GC are still unclear. In the study, we demonstrated that RNF168 expression was remarkably down-regulated in human GC tissues, and its low expression showed worse overall survival rate in GC patients. Importantly, we here reported that RNF168 directly interacted with Ras homolog gene family member C (RHOC) and induced its ubiquitination to promote RHOC degradation. RHOC exhibited higher expression in human GC tissues, and its knockdown significantly restrained cell proliferation, migration and invasion in GC cell lines. Moreover, RHOC knockdown led to a significant reduction in GC tumor growth in a xenograft mouse model. Additionally, histone deacetylase 1 (HDAC1) was found to be markedly decreased in GC cells with RHOC knockdown. Intriguingly, RHOC suppression-ameliorated proliferative and migratory ability in GC cells were significantly diminished by HDAC1 over-expression. Our in vivo studies finally confirmed that RHOC inhibition dramatically reduced the lung metastasis in nude mice. Collectively, all our results demonstrated that RNF168 directly interacted with RHOC to induce its degradation via promoting its ubiquitination, contributing to the inhibition of cell proliferation and metastasis in GC through decreasing HDAC1. Thus, targeting RNF168/RHOC/HDAC1 axis might be promising to develop effective therapies for GC treatment.
- Subjects :
- Male
0301 basic medicine
Lung Neoplasms
Ubiquitin-Protein Ligases
Biophysics
RhoC
Down-Regulation
Mice, Nude
Histone Deacetylase 1
Real-Time Polymerase Chain Reaction
Biochemistry
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
Ubiquitin
Cell Movement
Stomach Neoplasms
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Metastasis
Molecular Biology
Cell Proliferation
Mice, Inbred BALB C
Gene knockdown
biology
Cell growth
Chemistry
Ubiquitination
Cancer
Cell Biology
medicine.disease
Immunohistochemistry
Xenograft Model Antitumor Assays
HDAC1
Up-Regulation
Gene Expression Regulation, Neoplastic
030104 developmental biology
rhoC GTP-Binding Protein
Cell culture
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Disease Progression
biology.protein
Cancer research
Signal Transduction
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 557
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....0bd413ced5986581b2ea3bbff11f5b70