Abstract
Purpose: To investigate the role of FOXQ1 in the progression of epithelial ovarian cancer and the underlying mechanism.
 Methods: Forkhead Box Q1 overexpression was evaluated by quantitative reverse-transcription (qRTPCR) in clinical epithelial ovarian cancer samples and cell lines. Proliferation, migration, and invasion of cancer cells were determined using CCK8, wound healing and transwell assay.
 Results: FOXQ1 depletion inhibited the proliferation, migration, and invasion of `epithelial ovarian cancer cells. Moreover, FOXQ1 overexpression increased the amount of cells in S phase of the cell cycle, and FOXQ1 knockdown arrested cells inG1 phase. Results from ChIP and luciferase reporter assays showed that FOXQ1 was able to bind SIRT1 promoters. In addition, it was involved in sustaining the stability of nuclear factor erythroid derived 2-like 2 (NRF2) by decreasing its acetylation (p < 0.01), which was mediated by SIRT1. The data also demonstrated that NRF2 promotes proliferation, migration, and invasion of cancer cells upon FOXQ1 overexpression.
 Conclusion: Forkhead Box Q1 contributes to the progression of epithelial ovarian cancer partly via SIRT1/NRF2 signaling pathway, this highlighting a novel strategy for treating epithelial ovarian cancer.
Highlights
Ovarian cancer is one of the most common gynecological cancers [1]
Previous studies showed that FOXQ1 upregulated SIRT1 (Sirtuin 1) in esophageal cancer cells[12], suggesting that FOXQ1 might be involved in progression of epithelial ovarian cancer by targeting the SIRT1/nuclear factor erythroid derived 2-like 2 (NRF2) signaling pathway
FOXQ1 was highly expressed in epithelial ovarian cancer tissues and cell lines colony formation assay confirmed that FOXQ1 overexpression increased the proliferation of OVCAR4 cells and COV644 cells, whereas FOXQ1 knockdown caused the opposite effect(Figure 2 D).Consistently, the cell cycle of OVCAR4 and COV644 was influenced by the expression of FOXQ1 (Figure 2 E)
Summary
Ovarian cancer is one of the most common gynecological cancers [1]. High-grade serous epithelial ovarian cancer is highly aggressive with a poor prognosis, often leading to rapid progression and high mortality[2]. A previous report showed that knockdown of FOXQ1 inhibited the cell cycle and decreased the invasion of an ovarian cancer cell line [8]. Previous studies showed that FOXQ1 upregulated SIRT1 (Sirtuin 1) in esophageal cancer cells[12], suggesting that FOXQ1 might be involved in progression of epithelial ovarian cancer by targeting the SIRT1/NRF2 signaling pathway. The effect of FOXQ1 on proliferation, migration, and invasion of epithelial cancer cells and the relationship between FOXQ1 and the SIRT1/NRF2 signaling pathway. Subsequent to the overexpression or knockdown of FOXQ1 or NRF2 incubation, OVCAR4 and COV644 cells were seeded into 6-well plates, incubated with DAPI OVCAR4 cells were seeded into 24well plates and transfected with pGL3-promoter vector using FuGENE HD (Roche, Basile, Switzerland; catalog number: E2311).
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