Down-regulation of TRIB3 inhibits the progression of ovarian cancer via MEK/ERK signaling pathway
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PRIMARY RESEARCH
Cancer Cell International Open Access
Down-regulation of TRIB3 inhibits the progression of ovarian cancer via MEK/ERK signaling pathway Shuang Wang1,2, Caixia Wang1,2, Xiao Li1,2, Yuexin Hu1,2, Rui Gou1,2, Qian Guo1,2, Xin Nie1,2, Juanjuan Liu1,2, Liancheng Zhu1,2 and Bei Lin1,2*
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 downregulation 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. Keywords: TRIB3, Ovarian cancer, Prognosis, MEK/ERK, EMT
*Correspondence: [email protected] 1 Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, No. 36, Sanhao Street, Heping District, Liaoning 110004, China Full list of author information is available at the end of the article
Background Among gynecological malignancies, ovarian cancer has the highest mortality rate, and poses serious threat to the health of women. The onset of the disease is insidious, and most patients who receive treatment are in the advanced stage of ovarian cancer.
© The Author(s) 2020. This article is licensed under a C
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