Systematic Pan-Cancer Analysis and Experimental Verification Identify FOXA1 As An Immunological and Prognostic Biomarker In Epithelial Ovarian Cancer

Abstract Background: Epithelial ovarian cancer (EOC) has the lowest survival rate among female reproductive cancers present with symptoms of aggressive malignancies, poor prognosis, drug resistance and postoperative recurrence. The majority of patients with EOC are diagnosed at an advanced stage due to the therapeutic challenges including lack of early diagnosis and effective therapeutic targets for EOC.Methods: Pan-cancer analyses were performed to explore the features of Forkhead box (FOX) A1 (FOXA1) using data from TCGA and GTEx database. R package “clusterprofiler” was used to perform the enrichment analysis of FOXA1 in EOC. Data downloaded from Drug Sensitivity in Cancer (GDSC) database were used to evaluate the association between FOXA1 and anti-tumor drug sensitivity. In experimental verification, FOXA1 expression was detected using qRT-PCR and Western blot assays. Western blot, immunofluorescence staining and transwell assays were used to assess the influence of FOXA1 silencing on epithelial-mesenchymal transition (EMT) of EOC cellsResults: We found that FOXA1 was highly expressed in EOC and predicted poorer survival of EOC patients. We observed that FOXA1 expression was positively correlated EMT related pathways. Through experimental verification, we found the underlying function of FOXA1 to promote EMT in ovarian cancers. Results from western blot, immunofluorescence staining and transwell assays showed that FOXA1 silencing impeded the progression of EMT and invasiveness of the cancer cells. Furthermore, CCK-8 and invasion assays suggested that siRNA-FOXA1 attenuated the ability of cancer cells to metastasize and proliferate. Dual-luciferase reporter assays confirmed the binding activity of FOXA1 to the promoter of connective tissue growth factor (CTGF). In addition, we found that FOXA1 was closely correlated immunosuppressive microenvironment of EOC. High FOXA1 expression may contribute to resistance of many anti-cancer drugs.Conclusions: Our results predict and validate the function of FOXA1 in promoting EMT and the progression of disease in EOC. Targeting FOXA1 may improve the sensitivity of EOC treatment.

Download Full-text

Chemotherapeutic drug sensitivity of primary cultures of epithelial ovarian cancer cells from patients in relation to tumour characteristics and therapeutic outcome

Acta Oncologica ◽

10.3109/0284186x.2013.794956 ◽

2013 ◽

Vol 53 (2) ◽

pp. 242-250 ◽

Cited By ~ 6

Author(s):

Anne von Heideman ◽

Bengt Tholander ◽

Birgitta Grundmark ◽

Stefan Cajander ◽

Eva Gerdin ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Drug Sensitivity ◽

Primary Cultures ◽

Therapeutic Outcome ◽

Ovarian Cancer Cells ◽

Chemotherapeutic Drug ◽

Tumour Characteristics

Download Full-text

Overexpression of Long Noncoding RNA H19 Downregulates miR-140-5p and Activates PI3K/AKT Signaling Pathway to Promote Invasion, Migration and Epithelial-Mesenchymal Transition of Ovarian Cancer Cells

BioMed Research International ◽

10.1155/2021/6619730 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Hao Xu ◽

Yuan Ding ◽

Xiangying Yang

Keyword(s):

Ovarian Cancer ◽

Western Blot ◽

Cancer Cells ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Akt Signaling Pathway ◽

Mesenchymal Transition

Objective. The abnormal expression of LncRNA H19 and miR-140-5p has been linked to ovarian cancer (OC). Whether H19 directly regulates miR-140-5p in ovarian cancer cells has been unclear. In this study, we deeply explored the relationship between H19 and miR-140-5p in ovarian cancer and the mechanism of action in regulating OC progression. Methods. A total of 66 patients with OC admitted to the hospital from June 2017 to June 2019 were selected as the research group (RG), and meanwhile, 60 cases of healthy subjects were selected as the control group (CG). In addition, OC cells and normal ovarian epithelial cells were used to detect H19 and miR-140-5p expression levels and to analyze the effect of H19 on OC cells. The activation of the PI3K/AKT pathway and downstream proteins were analyzed by western blot. Results. H19 was highly expressed while miR-140-5p was lowly expressed in OC patients and cell lines ( P < 0.050 ). The proliferation, invasion, migration ability, and epithelial-mesenchymal transition (EMT) of OC cells were reduced after inhibiting H19 expression, and the apoptosis rate was increased. Transfection of cells with miR-140-5p mimics brought opposite effects. Online prediction and dual-luciferase reporter (DLR) confirmed that H19 directly binds miR-140-5p. Western blot assay indicated overexpression activated the PI3K/AKT signaling pathway in OC cells. Moreover, overexpression promoted tumor growth in nude mice and was suppressed by PI3K inhibitor. Conclusion. LncRNA H19 downregulation of miR-140-5p to activate the PI3K/AKT signaling pathway and promote the proliferation, invasion, migration and EMT of OC.

Download Full-text

FOXQ1 promotes proliferation and metastasis of epithelial ovarian cancer via activation of SIRT1/NRF2 signaling pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i7.5 ◽

2021 ◽

Vol 18 (7) ◽

pp. 1397-1404

Author(s):

Yinfeng Lv ◽

Rongxia He ◽

Jia Lu ◽

Aihong Wei ◽

Ruijuan Chen

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Forkhead Box ◽

Nrf2 Signaling Pathway

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.

Download Full-text

ROS production is required for follicle-stimulating hormone-induced Nrf2 activation in human epithelial ovarian cancer cells

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2012.00935 ◽

2013 ◽

Vol 32 (9) ◽

pp. 935-939

Author(s):

Jie MA ◽

Qian-qian WANG ◽

Hong LIAO ◽

Yong-bin YANG ◽

Zhi-jun JIN ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Follicle Stimulating Hormone ◽

Ovarian Cancer Cells ◽

Ros Production ◽

Nrf2 Activation ◽

Stimulating Hormone

Download Full-text

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00775-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Huan Lu ◽

Guanlin Zheng ◽

Xiang Gao ◽

Chanjuan Chen ◽

Min Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Rna Binding ◽

Erk Signaling ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Download Full-text

Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02274-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Qingjuan Meng ◽

Ningning Wang ◽

Guanglan Duan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Invasion And Migration ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna

Abstract Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

Download Full-text