Identification and validation of differentially expressed proteins in epithelial ovarian cancers using quantitative proteomics

Abstract

Ovarian cancer is the most lethal gynecological malignant tumor because of its high recurrence rate. In the present work, in order to find new therapeutic targets, we identified 8480 proteins in thirteen pairs of ovarian cancer tissues and normal ovary tissues through quantitative proteomics. 498 proteins were found to be differentially expressed in ovarian cancer, which involved in various cellular processes, including metabolism, response to stimulus and biosynthetic process. The expression levels of chloride intracellular channel protein 1 (CLIC1) and lectin galactoside-binding soluble 3 binding protein (LGALS3BP) in epithelial ovarian cancer tissues were significantly higher than those in normal ovary tissues as confirmed by western blotting and immunohistochemistry. The knockdown of CLIC1 in A2780 cell line downregulated expression of CTPS1, leading to the decrease of CTP and an arrest of cell cycle G1 phase, which results into a slower proliferation. CLIC1-knockdown can also slow down the tumor growth in vivo. Besides, CLIC1-knockdown cells showed an increased sensitivity to hydrogen peroxide and cisplatin, suggesting that CLIC1 was involved in regulation of redox and drug resistance in ovarian cancer cells. These results indicate CLIC1 promotes tumorgenesis, and is a potential therapeutic target in epithelial ovarian cancer treatment.

CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer

“…As noted above, possible functional roles in tumor progression are incompletely understood and may differ depending upon the tumor type. In EOC, CLIC1 may be involved in cell cycle regulation and drug resistance 30 , while CLIC4 may have roles in fibroblast activation 29 . While CLIC1 has generally been associated with tumor progression in prior studies 32 , 34 , 38 , there are some contradictions regarding the role of CLIC4 in tumors.…”

“…Other studies have indicated that CLIC1 and CLIC4 may play roles in altering the EOC tumor microenvironment and affecting EOC tumor progression. CLIC4 regulated TGFβ-mediated activation of fibroblasts in EOC 29 and knocking down CLIC1 arrested EOC cell division at the G1 phase, inhibited xenograft growth in vivo , and increased susceptibility of the EOC cells to cisplatin and ROS exposure 30 .…”

Intracellular Chloride Channels: Novel Biomarkers in Diseases

“…CLIC1 is overexpressed in several cancers including liver cancer, gall bladder cancer, pancreatic ductal adenocarcinoma, glioma, breast cancer, nasopharyngeal carcinoma, and gastric cancer to name a few (Wulfkuhle et al, 2002;Petrova et al, 2008;Chang et al, 2009;Wang et al, 2009Wang et al, , 2018Tang et al, 2012;Wei et al, 2015;Jia et al, 2016;Qu et al, 2016). It is known to play a role in cell viability, possibly by modulating mitochondrial function.…”

“…Along with CLIC4, CLIC1 is a promising biomarker for epithelial ovarian cancer where its expression predicts patient survival (Singha et al, 2018). CLIC1 is shown to regulate the redox-sensitivity of ovarian cancer cells and is predicted to be a potential marker for lymphoblastic leukemia (Qu et al, 2016;Dehghan-Nayeri et al, 2017;Singha et al, 2018). Modulation of CLIC1 expression by micro RNA, hsa-mir-372 predicts the poor prognosis of patients affected with gall bladder cancers (Zhou et al, 2017) and is important for the migration and invasion of gall bladder cancer cells (He et al, 2018).…”

Association Between BMI and DNA Methylation in Blood or Normal Adult Breast Tissue: A Systematic Review

“…Other CpG sites located in CPT1A (cg17058475), ABCG1 (cg27243685, cg01881899 and cg10192877) and LGALS3BP (cg25178683, cg11202345, cg14870271, cg17836612 and cg27470213) were also identified in some of the studies. In the literature, the expression of CPT1A, ABCG1, SREBF1 and LGALS3BP has been associated with obesity (50-54) and linked to various cancers (55)(56)(57)(58)(59)(60)(61)(62), including breast cancer (63-69) adding plausibility to the findings. Indeed, CPT1A was recently found to be up-regulated in co-cultured adipocytes isolated from human breast adipose tissue with hormone receptor-positive or -negative breast cancer cells (70).…”