scholarly journals Effects of activating GABAB1 receptor on proliferation, migration, invasion and epithelial-mesenchymal transition of ovarian cancer cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Jun Gao ◽  
Yao Gao ◽  
Shixin Lin ◽  
Xia Zou ◽  
Yukai Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Mesenchymal Transition ◽  
Skov3 Cells ◽  
Lower Expression ◽  
E Cadherin

Abstract Objective This study aimed to explore the effects of activating GABAB1 receptor by baclofen on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ovarian cancer cells. Results One hundred μmol/L, 200 μmol/L and 300 μmol/L were selected as low, medium and high baclofen concentrations respectively. Cells were divided into four groups: Control, 100 μmol/L, 200 μmol/L and 300 μmol/L. Compared with the control group, the viability, colony formation, migration and invasion of SKOV3 cells were inhibited, and the apoptosis of SKOV3 cells were enhanced significantly at 200 μmol/L and 300 μmol/L baclofen. Moreover, they changed significantly with the increase of baclofen concentration. Compared with the control group, the expression of E-cadherin and GABAB1 increased and the N-cadherin expression decreased significantly in 200 μmol/L and 300 μmol/L groups. Higher concentration of baclofen induced higher expression of E-cadherin and lower expression of N-cadherin. Conclusion Baclofen inhibited the proliferation, cloning, migration, invasion and EMT of ovarian cancer cells by activating GABAB1 receptor. These results might contribute a lot to clarify the role and possible mechanism of GABAB1 receptor in ovarian cancer.

scholarly journals Tripartite Motif 16 Inhibits the Migration and Invasion in Ovarian Cancer Cells

2017 ◽  
Vol 25 (4) ◽  
pp. 551-558 ◽  
Author(s):  
Hongwei Tan ◽  
Jin Qi ◽  
Guanghua Chu ◽  
Zhaoyang Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Hedgehog Signaling ◽  
Epithelial Mesenchymal Transition ◽  
Coiled Coil ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Tripartite Motif

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite motif (TRIM) protein family, has been shown to play a role in tumor development and progression. However, the role of TRIM16 in ovarian cancer has never been revealed. Thus, in this study, we investigated the roles and mechanisms of TRIM16 in ovarian cancer. Our results demonstrated that TRIM16 expression was low in ovarian cancer cell lines. In addition, overexpression of TRIM16 significantly inhibited the migration and invasion in vitro, as well as suppressed the epithelial‐mesenchymal transition (EMT) phenotype in ovarian cancer cells. Furthermore, overexpression of TRIM16 greatly inhibited the protein expression levels of Shh, Smo, Ptc, Gli-1, MMP2, and MMP9 in ovarian cancer cells. Taken together, these results strongly suggest that TRIM16 inhibits the migration and invasion via suppressing the Sonic hedgehog signaling pathway in ovarian cancer cells. Thus, TRIM16 may be a novel potential therapeutic target for ovarian cancer.

215 SNAIL AND SLUG, MARKERS OF EPITHELIAL MESENCHYMAL TRANSITION, APPEARED TO BE ALTERED BY ALKYL-PHENOLS, BISPHENOL A AND NONYL-PHENOL, IN OVARIAN CANCER CELLS EXPRESSING ESTROGEN RECEPTORS

2015 ◽  
Vol 27 (1) ◽  
pp. 198 ◽  
Author(s):  
Y.-S. Kim ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cells ◽  
Rt Pcr ◽  
Nonyl Phenol ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Emt Markers ◽  
E Cadherin

The ovary is the important organ to produce oocytes. Any disorder will affect embryo production. Ovarian cancer is one of gynecologic cancers in women which can affect ovarian functions. Oestradiol (E2) may be involved in ovarian cell growth and epithelial-mesenchymal transition (EMT) for diverse functions. EMT is an important process in embryo development and tumour migration or progression. Bis-phenol A (BPA) and nonyl-phenol (NP) have an estrogenic property, which can be suspected as endocrine disrupting chemicals (EDC). In this study, it has been examined whether BPA and NP can cause EMT process and migration in BG-1 ovarian cancer cells. To confirm the effect of these EDCs, BG-1 ovarian cancer cells were cultured and treated with DMSO (0.1%), E2 (10–7 M), BPA (10–6 M) and NP (10–6 M) for 0, 6, and 24 h. The mRNAs were extracted to perform reverse-transcription (RT)-PCR and the changes in the mRNA expressions were analysed by ANOVA test. Following treatments with BPA and NP, alterations of EMT markers; that is, vimentin and E-cadherin, were examined at mRNA levels by RT-PCR. The levels of vimentin were up-regulated by E2, BPA, or NP in a time-dependent manner. In addition, transcriptional factors of EMT response, i.e. snail and slug, were enhanced by these treatments more than 2 times. BG-1 cells were exposed to these EDCs for 0, 24, and 48 h. Vimentin and snail proteins were induced by E2, BPA, or NP, while the expression of E-cadherin was decreased by them. To reveal that this EMT response is affected by oestrogen receptor (ER), the cells were treated with these EDCs in the presence of an ER antagonist, ICI 182 780 (10–6 M). Treatment with ICI 182 780 reversed EDC-induced alteration of these EMT markers, E-cadherin, vimentin, and snail. Since EMT response can cause metastasis, a scratch assay was performed to show migration caused by BPA or NP. BPA or E2 enhanced migratory capability of these BG-1 cells. Taken together, these results indicate that BPA and NP, potential EDC, may have an ability to influence ovarian cancer metastasis via regulating snail and slug genes in ER-positive ovarian cancers. In a future study, their effects in inducing EMT and migration will be tested in a xenograft mouse model.This work was supported by a grant from the Next-Generation BioGreen 21 Program (no. PJ009599), Rural Development Administration, Republic of Korea.

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

Blood ◽  
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.

scholarly journals MicroRNA-30 inhibits the growth of human ovarian cancer cells by suppressing RAB32 expression

2022 ◽  
Vol 36 ◽  
pp. 205873842110586
Author(s):  
Yan Zhang ◽  
Min Zhou ◽  
Kun Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Transcriptional Level ◽  
Human Ovarian Cancer ◽  
Mesenchymal Transition

Introduction MicroRNAs (miRs) exhibit the potential to act as therapeutic targets for the management of human cancers including ovarian cancer. The role of microRNA-30 (miR-30) via modulation of RAB32 expression has not been studied in ovarian cancer. Consistently, the present study was designed to characterize the molecular role of miR-30/RAB32 axis in human ovarian cancer. Methods Cell viability was determined by MTT assay. Expression analysis was carried out by qRT-PCR. Dual luciferase assay was used to confirm the interaction between miR-30 and RAB32. Scratch-heal and transwell chamber assays were used to monitor the cell migration and invasion. Western blotting and immunofluorescence assays were used to determine the protein expression. Results The results revealed significant ( p < 0.05) downregulation of miR-30 in human ovarian cancer cell lines. Overexpression of miR-30 in ovarian SK-OV-3 and A2780 cancer cells significantly ( p < 0.05) inhibited their proliferation. Besides, ovarian cancer cells overexpressing miR-30 showed significantly ( p < 0.05) lower migration and invasion. The miR-30 upregulation also altered the expression pattern of marker proteins of epithelial–mesenchymal transition in ovarian cancer cells. In silico analysis predicted RAB32 as the molecular target of miR-30 at post-transcriptional level. The silencing of RAB32 mimicked the tumor-suppressive effects of miR-30 overexpression in ovarian cancer cells. Nonetheless, overexpression of RAB32 could prevent the tumor-suppressive effects of miR-30 on SK-OV-3 and A2780 cancer cells. Conclusion Taken together, the results suggest the tumor-suppressive role of miR-30 and point towards the therapeutic utility of miR-30/RAB32 molecular axis in the management of ovarian cancer

scholarly journals PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Gou ◽  
Yuexin Hu ◽  
Ouxuan Liu ◽  
Hui Dong ◽  
Lingling Gao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Phosphoglycerate Kinase ◽  
Expression Level ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Research Perspective ◽  
New Research

Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (PGK1), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the PGK1 expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.

scholarly journals MiR-15a-5p Inhibits Migration and Invasion of Ovarian Cancer Cells by Targeting PELP1

2020 ◽  
Author(s):  
Yujia Yang ◽  
Li Yuan ◽  
Bing Yang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Reporter Assays

Abstract Background: Ovarian cancer is one of the most common malignancy of the female reproductive system. Hsa‐miR‐15a‐5p (miR‐15a-5p) has been reported with tumor‐suppressing roles in various cancers. This study aims to determine the role of miR-15a-5p during the progression of ovarian cancer. Methods: We used bioinformatics, luciferase reporter assays, wound-healing, transwell invasion assays, quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot to dissect the molecular mechanism of how miR-15a-5p may cause metastasis in ovarian cancer. Results: The upregulation of miR‐15a-5p inhibited growth, migration and invasion in ovarian cancer cells. Furthermore, miR-15a-5p suppressed epithelial mesenchymal transition (EMT) of ovarian cancer cell in vitro, evidenced by expression alteration of E‐cadherin and vimentin. Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) was identified as the direct target of miR-15a-5p and downregulated by miR-15a-5p. The inhibitory effect of miR-15a-5p on migration, invasion and EMT was rescued by PELP1. Additionally, downregulation of PELP1 mimicked the suppressive impact of miR-15a-5p on ovarian carcinoma cells. Conclusions: Our data indicated that miR-15a-5p inhibited migration, invasion and EMT of ovarian cancer cells by targeting PELP1, which might relate to the progression and metastasis of ovarian cancer.

scholarly journals Aligned Collagen-CNT Nanofibrils and the Modulation Effect on Ovarian Cancer Cells

2021 ◽  
Vol 5 (6) ◽  
pp. 148
Author(s):  
Wen Li ◽  
Naiwei Chi ◽  
Elwin D. Clutter ◽  
Bofan Zhu ◽  
Rong R. Wang
Keyword(s):  
Ovarian Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Tissue Regeneration ◽  
Epithelial Mesenchymal Transition ◽  
Dimensional Structure ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
One Dimensional ◽  
Skov3 Cells

Fibrillar collagen is a one-dimensional biopolymer and is the most abundant structural protein in the extracellular matrix (ECM) of connective tissues. Due to the unique properties of carbon nanotubes (CNTs), considerable attention has been given to the application of CNTs in developing biocomposite materials for tissue engineering and drug delivery. When introduced to tissues, CNTs inevitably interact and integrate with collagen and impose a discernible effect on cells in the vicinity. The positive effect of the collagen-CNT (COL-CNT) matrix in tissue regeneration and the cytotoxicity of free CNTs have been investigated extensively. In this study, we aimed to examine the effect of COL-CNT on mediating the interaction between the matrix and SKOV3 ovarian cancer cells. We generated unidirectionally aligned collagen and COL-CNT nanofibrils, mimicking the structure and dimension of collagen fibrils in native tissues. AFM analysis revealed that the one-dimensional structure, high stiffness, and low adhesion of COL-CNT greatly facilitated the polarization of SKOV3 cells by regulating the β-1 integrin-mediated cell–matrix interaction, cytoskeleton rearrangement, and cell migration. Protein and gene level analyses implied that both collagen and COL-CNT matrices induced the epithelial–mesenchymal transition (EMT), and the COL-CNT matrix prompted a higher level of cell transformation. However, the induced cells expressed CD44 at a reduced level and MMP2 at an increased level, and they were responsive to the chemotherapy drug gemcitabine. The results suggested that the COL-CNT matrix induced the transdifferentiation of the epithelial cancer cells to mature, less aggressive, and less potent cells, which are inapt for tumor metastasis and chemoresistance. Thus, the presence of CNT in a collagen matrix is unlikely to cause an adverse effect on cancer patients if a controlled dose of CNT is used for drug delivery or tissue regeneration.

scholarly journals Exosomal microRNA-205 is involved in proliferation, migration, invasion, and apoptosis of ovarian cancer cells via regulating VEGFA

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijun Wang ◽  
Fei Zhao ◽  
Zhongqing Xiao ◽  
Liang Yao
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Diagnostic Value ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Skov3 Cells ◽  
Gene Assay ◽  
The Impact

Abstract Background Recently, the impact of microRNAs (miRNAs) and exosome on ovarian cancer has been assessed in many studies. We aim to explore the mechanism of exosomes transferring miR-205 in ovarian cancer, and confirm its diagnostic value in ovarian cancer. Methods The expression of miR-205 of ovarian cancer patients and healthy people was detected by RT-qPCR, and the diagnostic value of miR-205 was evaluated. The exosomes derived from SKOV3 cells were identified. Ovarian cancer SKOV3 donor cells and receptor cells were used to measure the proliferation, migration, invasion, apoptosis and cell cycle by a series of experiments. The binding site between miR-205 and vascular endothelial growth factor A (VEGFA) was evaluated by bioinformatics tool and dual-luciferase reporter gene assay. Results MiR-205 was up-regulated in ovarian cancer, and up-regulated miR-205 could enhance the risk of ovarian cancer and was one of its risk factors. After SKOV3 cells-derived exosomes were transiently introduced with miR-205 mimics, the cell proliferation, migration and invasion in ovarian cancer were elevated, the apoptosis of ovarian cancer cells was attenuated, and the epithelial–mesenchymal transition (EMT) protein E-cadherin was down-regulated, while Vimentin was elevated. VEGFA was identified to be a target gene of miR-205. Conclusion This study suggests that exosomes from donor ovarian cancer cell SKOV3 shuttled miR-205 could participate in the regulation of the proliferation, migration, invasion, apoptosis as well as EMT progression of receptor SKOV3 cells by targeting VEGFA.

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