Long Noncoding RNA E2F4as Promotes Progression and Predicts Patient Prognosis in Human Ovarian Cancer

(1) Background: LncRNAs could be a promising biomarker to predict the prognosis of various cancers. The significance of E2F4antisense lncRNA remains unclear in cancer. In this study, we examined the expression level of E2F4as in the serum of ovarian cancer patients and the functional role of E2F4as. (2) Methods: Serum samples were obtained from 108 OC patients and 32 normal patients to measure the expression of E2F4as in the serum. Ovarian cancer cells were used to investigate the role of E2F4as in cell proliferation, invasion, migration and apoptosis, and the expression of E2F4as was knocked down using RNA interference. In addition, E2F4as knockdown cell lines were used in in vivo experiments. (3) Results: The expression of E2F4as was significantly higher in the serum of OC patients than in that of control patients (p < 0.05). The knockdown of E2F4as in ovarian cancer cells led to a decrease in cell proliferation, invasion and migration and an increase in apoptosis. E2F4as knockdown also reduced the expression of epithelium–mesenchymal metastasis (EMT) genes. (4) Conclusion: These findings highlight the clinical significance of E2F4as in predicting the prognosis of OC patients and suggest its potential in promoting tumour aggressiveness by the regulation of EMT-related mechanisms.

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microRNA-4488 in extracellular vesicles derived from marrow mesenchymal stem cells suppresses ABHD8 to inhibit ovarian cancer progression

10.21203/rs.3.rs-125335/v1 ◽

2020 ◽

Author(s):

Lei Chang ◽

Junying Zhou ◽

Wanjia Tian ◽

Mengyu Chen ◽

Ruixia Guo ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Progression ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Invasion And Migration ◽

And Migration

Abstract Background Extracellular vesicle (EV) that delivered microRNAs (miRNAs) have been found as the important biomarkers participating in the pathological mechanism of ovarian cancer. Consequently, this study sought to examine the underlying mechanism of mesenchymal stem cell (MSC)-derived EVs containing miR-4488 in ovarian cancer. Methods The normal ovarian tissues and ovarian cancer tissues were extracted, and the information of MSC-EV miRNA was obtained by Bioinformatics analysis. RT-qPCR and western blot analysis were applied to detect miR-4488 and α/β-hydrolase domain-containing (ABHD)8 expression followed by determination of relationship between miR-4488 and ABHD8 by dual-luciferase reporter assay. After transfection with different plasmids and treatment with DMSO or GW4869 (inhibitor of EV), the regulatory roles of MSC-EV-miR-4488 in invasion, proliferation, apoptosis, and migration of cancer cells were explored. Besides, xenograft tumor in nude mice was conducted to explore the role of miR-4488 and ABHD8 in ovarian cancer in vivo. Results miR-4488 was poorly expressed and ABHD8 was highly expressed in ovarian cancer cells and tissues. ABHD8 was a target gene of miR-4488 while the knockdown of ABHD8 resulted in the suppression of proliferation, invasion, and migration while promoting the apoptosis of cancer cells. Functionally, MSC-EV-derived miR-4488 inhibited the expression of ABHD8. Additionally, miR-4488 over-expressed in MSC-EVs inhibited the cell proliferation, invasion, and migration through down-regulation of ABHD8 expression. At last, these in vitro findings were also confirmed in vivo. Conclusion To summarize, miR-4488 overexpressed in MSC-EVs suppressed ABHD8 expression to inhibit the cancer cell proliferation, invasion, and migration, thus suppressing ovarian cancer.

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The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Tumor Biology ◽

10.1177/1010428317705508 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770550 ◽

Cited By ~ 4

Author(s):

Yi Li ◽

Ming Xiao ◽

Fangchun Guo

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Conditioned Medium ◽

Umbilical Vein ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Human Umbilical Vein ◽

Tumor Tissues

SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.

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Complement Component 3 (C3) Is a Mediator of Epithelial-Mesenchymal Transition (EMT)

Blood ◽

10.1182/blood.v124.21.1421.1421 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1421-1421

Author(s):

Min Soon Cho ◽

Qianghua Hu ◽

Rajesha Rupaimoole ◽

Anil Sood ◽

Vahid Afshar-Kharghan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Mouse Embryos ◽

Ovarian Cancer Cells ◽

Mesenchymal Transition ◽

E Cadherin

Abstract We have shown that complement component 3 (C3) is expressed in malignant ovarian epithelial cells and enhances cell proliferation in vitro and tumor growth in vivo. C3 is secreted by cancer cells into the tumor microenvironment and promotes tumor growth through an autocrine loop. To understand the mechanism of upregulation of C3 expression in malignant epithelial cells, we studied the transcriptional regulation of C3, and found that TWIST1, a major regulator of EMT, binds to the C3 promoter and regulates C3 transcription. Knockdown of the TWIST1 gene reduced C3 mRNA, and TWIST1 overexpression increased C3 mRNA. TWIST1 promotes epithelial-mesenchymal transition (EMT) during normal development and in metastasis of malignant tumors. An important marker of EMT is a reduction in the surface expression of E-cadherin on cells facilitating migration and invasion of these cells. TWIST1 is a transcriptional repressor of E-cadherin; and because TWIST1 increases C3 expression, we investigated whether C3 is also a negative regulator of E-cadherin expression. We overexpressed C3 in ovarian cancer cells by stable transduction of lentivirus carrying C3 cDNA. Overexpression of C3 was associated with 32% reduction in the expression of E-cadherin resulting in enhanced migration ability of cells by 2.3 folds and invasiveness by 1.75 folds, as compared to control cells transduced with control lentivirus. To investigate whether TWIST1-induced reduction in E-cadherin is C3-mediated or not, we studied the effect of TWIST1 overexpression simultaneous with C3 knockdown in ovarian cancer cells. Overexpression of TWIST1 alone resulted in 70% reduction in E-cadherin mRNA and this was completely reversed after simultaneous C3 knockdown in these cells. To investigate the correlation between C3 and TWIST1 in vivo, we studied the co-expression of these two proteins in mouse embryos (physiologic EMT) and in malignant tumors (pathologic EMT). Given the role of EMT in embryogenesis we immunostained mouse embryos at different stages of development, using antibodies against TWIST1 or C3. Transverse section of 9.5-day post-coitum (9.5dpc) mouse embryos showed co-expression of TWIST1 and C3 in otocyst (ot) and hindbrain (hb) of neural crest. In the whole-mounted 11.5dpc mouse embryos, C3 and TWIST1 were co-expressed in limb buds. Given the role of EMT in malignancy, tumors induced in mice after intraperitoneal injection of murine ovarian cancer cells were resected and immunostained for C3 and TWIST1 proteins. TWIST1 and C3 co-localized at tumor edges, where EMT and tumor cells migration occur. Taken together, these data provide evidence that TWIST1 regulates C3 expression, and C3 promotes EMT through E-cadherin. Disclosures No relevant conflicts of interest to declare.

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circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

10.21203/rs.2.23146/v1 ◽

2020 ◽

Author(s):

Qin Xu ◽

Bo Deng ◽

Manlin Li ◽

Yang Chen ◽

Li Zhuan

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Target Gene ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Competing Endogenous Rnas ◽

Cancer Tissues

Abstract Objective: circular RNAs (circRNAs) have been reported to be essential regulators of multiple malignant cancers. However, the functions of circRNAs in ovarian cancer need to be further explored. The aim of our study is to explore the role of circRNA-UBAP2 in ovarian cancer and its mechanism. Results: circRNA-UBAP2 was upregulated in ovarian cancer tissues and cell lines. Knockdown of circRNA-UBAP2 inhibited cell proliferation and promoted cell apoptosis, but circRNA-UBAP2 overexpressed got opposite results. In addition, circRNA-UBAP2 targeted miR-382-5p and downregulated its expression, PRPF8 was a target gene of miR-382-5p. Furthemore, circRNA-UBAP2/miR-382-5p/PRPF8 axis affected the proliferation, apoptosis and cell cycle of ovarian cancer through the mechanism of competing endogenous RNAs (ceRNA). Conclusion: circRNA-UBAP2 acted as a ceRNA to sponged miR-382-5p, increased the expression level of PRPF8, and prompted proliferation and inhibited apoptosis in ovarian cancer cells.

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circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

10.21203/rs.2.23146/v2 ◽

2020 ◽

Author(s):

Qin Xu ◽

Bo Deng ◽

Manlin Li ◽

Yang Chen ◽

Li Zhuan

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Target Gene ◽

Circular Rnas ◽

Ovarian Cancer Cells ◽

Competing Endogenous Rnas ◽

Cancer Tissues

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LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation

Bioscience Reports ◽

10.1042/bsr20171150 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 21

Author(s):

Jie Li ◽

Chen Yang ◽

Yinguang Li ◽

Aiyue Chen ◽

Li Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Apoptosis ◽

Colony Formation ◽

Sandwich Elisa ◽

Ovarian Cancer Cells ◽

Cancer Tissues ◽

Lncrna Gas5

Objective: Long noncoding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the present study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. Methods: Quantitative real-time PCR was used to detect mRNA level of lncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Western blotting was used to detect the protein level of lncRNA GAS5 potential target. Standard sandwich ELISA was used to quantify the level of inflammatory cytokines. The cells with stable expression of lncRNA GAS5 were injected into nude mice to study the effect of lncRNA GAS5 on tumorigenesis in vivo. Results: The expression of lncRNA GAS5 was significantly decreased in ovarian cancer tissues. Decrease in lncRNA GAS5 expression resulted in increased cell proliferation and colony formation and reduced ovarian cancer cell apoptosis. In contrast, exogenous overexpression of lncRNA GAS5 in ovarian cancer cells inhibited proliferation, colony formation, and apoptosis in ovarian cancer cells. In addition, the role of lncRNA GAS5 in ovarian cancer was associated with inflammasome formation and pyroptosis. Conclusion: These results suggested that lncRNA GAS5 acts as tumor suppressor and could be used as a potential treatment target for diagnosis and therapy of ovarian cancer.

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WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

10.21203/rs.3.rs-18963/v2 ◽

2020 ◽

Author(s):

Zi-Qing Shi ◽

Zi-Yan Chen ◽

Yao Han ◽

Heng-Yan Zhu ◽

Meng-Dan Lyu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Extracellular Signal ◽

And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

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Circ_MUC16 attenuates the effects of Propofol to promote the aggressive behaviors of ovarian cancer by mediating the miR-1182/S100B signaling pathway

BMC Anesthesiology ◽

10.1186/s12871-021-01517-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hao Yang ◽

Yunrui Guo ◽

Yecai Zhang ◽

Decai Wang ◽

Guoyun Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Lactate Production ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Aggressive Behaviors

Abstract Background Propofol is commonly used for anesthesia during surgery and has been demonstrated to inhibit cancer development, which is shown to be associated with deregulation of non-coding RNAs (ncRNAs). The objective of this study was to explore the role of circular RNA mucin 16 (circ_MUC16) in Propofol-mediated inhibition of ovarian cancer. Methods The expression of circ_MUC16, microRNA-1182 (miR-1182) and S100 calcium-binding protein B (S100B) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). The expression of S100B protein was checked by western blot. Cell proliferation was assessed by 3-(4, 5-di methyl thiazol-2-yl)-2, 5-di phenyl tetrazolium bromide (MTT) assay and colony formation assay. Glycolysis metabolism was assessed by glucose consumption, lactate production and ATP level. Cell migration and cell invasion were assessed by transwell assay. Cell migration was also assessed by wound healing assay. Animal study was conducted in nude mice to determine the role of circ_MUC16 in vivo. The relationship between miR-1182 and circ_MUC16 or S100B was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results Propofol inhibited ovarian cancer cell proliferation, glycolysis metabolism, migration and invasion, which were partly recovered by circ_MUC16 overexpression. Circ_MUC16 was downregulated in Propofol-treated ovarian cancer cells. Besides, circ_MUC16 knockdown enhanced the effects of Propofol to further inhibit tumor growth in vivo. MiR-1182 was a target of circ_MUC16, and circ_MUC16 knockdown-inhibited cell proliferation, glycolysis metabolism, migration and invasion were partly restored by miR-1182 inhibition. In addition, S100B was a target of miR-1182, and miR-1182-suppressed cell proliferation, glycolysis metabolism, migration and invasion were partly restored by S100B overexpression. Conclusion Circ_MUC16 overexpression alleviated the effects of Propofol to promote the aggressive behaviors of ovarian cancer by targeting the miR-1182/S100B network.

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WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

10.21203/rs.3.rs-18963/v1 ◽

2020 ◽

Author(s):

Zi-Qing Shi ◽

Zi-Yan Chen ◽

Yao Han ◽

Heng-Yan Zhu ◽

Meng-Dan Lyu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Growth Inhibitory ◽

Extracellular Signal ◽

And Migration

Abstract Background Wnt inducible signaling protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on proliferation and migration of ovarian cancer cells in vitro and in vivo . Results Immunohistochemistry and western blot results indicated that WISP2 was highly expressed in various ovarian tissues and cell lines. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells. WISP2 deletion promoted cell apoptosis and affected the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of extracellular signal-related kinase (p-ERK)1/2, as well as CEBPα and CEBPβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). Conclusion WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

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miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

10.21203/rs.3.rs-17850/v2 ◽

2020 ◽

Author(s):

Yunhe An ◽

Jun Zhang ◽

Yanjie Tian ◽

Baoming Li ◽

Xiaoyan Cheng ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Patients ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Reporter Assay ◽

Cancer Tissues ◽

Dual Luciferase Reporter Assay

Abstract Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.

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