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Cancer Cell International

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01-12-2020 | Ovarian Cancer | Primary research

Down-regulation of TRIB3 inhibits the progression of ovarian cancer via MEK/ERK signaling pathway

Authors: Shuang Wang, Caixia Wang, Xiao Li, Yuexin Hu, Rui Gou, Qian Guo, Xin Nie, Juanjuan Liu, Liancheng Zhu, Bei Lin

Published in: Cancer Cell International | Issue 1/2020

Abstract

Background

Tribbles pseudokinase 3 (TRIB3) protein is a pseudokinase which plays an important role in cellular stress, metabolism, and tumor progression. However, the expression and function of TRIB3 in ovarian cancer is unknown.

Methods

TRIB3 expression was detected by immunohistochemistry in the ovarian tissue samples. Following down-regulation of TRIB3 by siRNA, multiple aspects of ovarian cancer cells were detected by the MTT assay, flow cytometry, scratch test and Transwell. Additionally, changes in related molecules and the MEK/ERK pathway were detected by western blotting. Finally, many bioinformatic methods, websites and databases, such as gene set enrichment analysis (GSEA), DVAID, Genemania, TISIDB and cBioPortal were used to study the TRIB3.

Results

The expression level of TRIB3 was higher in ovarian epithelial malignant tumors as compared to other groups. Patients with a high expression level of TRIB3 had significantly shorter survival times,which was consistent with the results of analysis of the KM-plot database. Down-regulation of TRIB3 expression significantly inhibited the proliferation, invasion, and migration capabilities of ovarian cancer cells, and induced apoptosis and cell cycle arrest. Following TRIB3 siRNA transfection, expression levels of relative proteins were found to be decreased. Additionally, analysis in DAVID website and GSEA revealed that TRIB3 expression was associated with multiple biological processes. Protein phosphorylation levels of MEK and ERK also decreased following TRIB3-siRNA transfection. The Genemania website was used to analyze the proteins that interact with TRIB3. Analysis of TRIB3 in the TISIDB database and cBioPortal website showed that ovarian cancer patients with high levels of mutation in TRIB3 had poor prognosis, and that the expression of TRIB3 was related to immunomodulation.

Conclusions

The TRIB3 was highly expressed and promoting the malignant behavior of ovarian cancer cells by activating the MEK-ERK signaling pathway. It was also found to be associated with genetic variations and immune modulators.

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Title: Down-regulation of TRIB3 inhibits the progression of ovarian cancer via MEK/ERK signaling pathway
Authors: Shuang Wang
Caixia Wang
Xiao Li
Yuexin Hu
Rui Gou
Qian Guo
Xin Nie
Juanjuan Liu
Liancheng Zhu
Bei Lin
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Ovarian Cancer
Ovarian Cancer
Published in: Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-020-01509-z

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Abstract

Background

Methods

Results

Conclusions

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