Overexpression of CSN6 promotes the epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma.

Abstract

BACKGROUND AND AIM:

CSN6, as a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), has been previously reported to be increased in various cancers; however, its effect in hepatocellular carcinoma (HCC) remains unknown, which is the aim of present study, in terms of its explore the expression and role of CSN6 in HCC.

METHODS:

QRT-PCR, Western blot and immunohistochemistry (IHC) were used to examine the expression of CSN6. Kaplan-Meier survival analysis and univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of CSN6 expression in HCC patients. Furthermore, the biological function of CSN6 on HCC cell proliferation and migration was investigated through CCK-8, transwell migration and invasion assays. Besides, the associations between CSN6 and epithelial-mesenchymal transition (EMT) were determined.

RESULTS:

CSN6 was increased in HCC tissues, and its overexpression was found to be associated with a poor prognoses for HCC patients. Overexpression of CSN6 promoted processes of HCC cell proliferation, migration, and invasion, while these processes were inhibited when CSN6 was silenced. Additionally, CSN6 was found to promote EMT by inhibiting E-cadherin, which were significantly mitigated via upregulation of Snail as a result of MEK/ERK pathway activation.

CONCLUSIONS:

CSN6 up-regulation may play a contributory role in HCC metastasis and poor prognosis via activation of EMT, and may serve as an independent predictor for HCC prognosis.

• Authors: Ming Xu, Lonbo Zhen, Liumei Lin, Ke Wu, Yifan Wang, Xiujun Cai
• Journal: Clinics and research in hepatology and gastroenterology (Clin Res Hepatol Gastroenterol) Vol. 44 Issue 3 Pg. 340-348 (06 2020) ISSN: 2210-741X [Electronic] France
• PMID: 31422034 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens, CD
• Biomarkers, Tumor
• CDH1 protein, human
• COPS6 protein, human
• Cadherins
• Snail Family Transcription Factors
• COP9 Signalosome Complex

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Antigens, CD (metabolism)
• Biomarkers, Tumor (metabolism)
• COP9 Signalosome Complex (metabolism)
• Cadherins (metabolism)
• Carcinoma, Hepatocellular (metabolism, mortality, pathology, secondary)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition (physiology)
• Female
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms (metabolism, mortality, pathology)
• MAP Kinase Signaling System (physiology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Prognosis
• Proportional Hazards Models
• Snail Family Transcription Factors (metabolism)
• Up-Regulation