scholarly journals High LIN28A Expressing Ovarian Cancer Cells Secrete Exosomes That Induce Invasion and Migration in HEK293 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Vanessa A. Enriquez ◽  
Ellane R. Cleys ◽  
Juliano C. Da Silveira ◽  
Monique A. Spillman ◽  
Quinton A. Winger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Tumor Development ◽  
Hek293 Cells ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Epithelial ovarian cancer is the most aggressive and deadly form of ovarian cancer and is the most lethal gynecological malignancy worldwide; therefore, efforts to elucidate the molecular factors that lead to epithelial ovarian cancer are essential to better understand this disease. Recent studies reveal that tumor cells release cell-secreted vesicles called exosomes and these exosomes can transfer RNAs and miRNAs to distant sites, leading to cell transformation and tumor development. The RNA-binding protein LIN28 is a known marker of stem cells and when expressed in cancer, it is associated with poor tumor outcome. We hypothesized that high LIN28 expressing ovarian cancer cells secrete exosomes that can be taken up by nontumor cells and cause changes in gene expression and cell behavior associated with tumor development. IGROV1 cells were found to contain high LIN28A and secrete exosomes that were taken up by HEK293 cells. Moreover, exposure to these IGROV1 secreted exosomes led to significant increases in genes involved in Epithelial-to-Mesenchymal Transition (EMT), induced HEK293 cell invasion and migration. These changes were not observed with exosomes secreted by OV420 cells, which contain no detectable amounts of LIN28A or LIN28B. No evidence was found of LIN28A transfer from IGROV1 exosomes to HEK293 cells.

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

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.

scholarly journals Wnt5A and TGFβ1 Converges through YAP1 Activity and Integrin Alpha v Up-Regulation Promoting Epithelial to Mesenchymal Transition in Ovarian Cancer Cells and Mesothelial Cell Activation

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 237
Author(s):  
Zeinab Dehghani-Ghobadi ◽  
Shahrzad Sheikh Hasani ◽  
Ehsan Arefian ◽  
Ghamartaj Hossein
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Serous Ovarian Cancer ◽  
Mesenchymal Transition ◽  
Nuclear Shuttling

In this paper, we investigate whether Wnt5A is associated with the TGF-β1/Smad2/3 and Hippo-YAP1/TAZ-TEAD pathways, implicated in epithelial to mesenchymal transition (EMT) in epithelial ovarian cancer. We used 3D and 2D cultures of human epithelial ovarian cancer cell lines SKOV-3, OVCAR-3, CAOV-4, and different subtypes of human serous ovarian cancer compared to normal ovary specimens. Wnt5A showed a positive correlation with TAZ and TGFβ1 in high- and low-grade serous ovarian cancer specimens compared to borderline serous and normal ovaries. Silencing Wnt5A by siRNAs significantly decreased Smad2/3 activation and YAP1 expression and nuclear shuttling in ovarian cancer (OvCa) cells. Furthermore, Wnt5A was required for TGFβ1-induced cell migration and invasion. In addition, inhibition of YAP1 transcriptional activity by Verteporfin (VP) altered OvCa cell migration and invasion through decreased Wnt5A expression and inhibition of Smad2/3 activation, which was reverted in the presence of exogenous Wnt5A. We found that the activation of TGFβ1 and YAP1 nuclear shuttling was promoted by Wnt5A-induced integrin alpha v. Lastly, Wnt5A was implicated in activating human primary omental mesothelial cells and subsequent invasion of ovarian cancer cells. Together, we propose that Wnt5A could be a critical mediator of EMT-associated pathways.

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.

scholarly journals Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/β-catenin/SLUG axis

2020 ◽  
Vol 11 (8) ◽  
Author(s):  
Shixia Bu ◽  
Qian Wang ◽  
Junyan Sun ◽  
Xiao Li ◽  
Tingting Gu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Restraint Stress ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Chronic Restraint Stress ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Tumor Tissues

Abstract Chronic stress has been shown to facilitate progression of epithelial ovarian cancer (EOC), however, the neuro-endocranial mechanism participating in this process still remains unclear. Here, we reported that chronic restraint stress (CRS) promoted the abdominal implantation metastasis of EOC cells and the expression of epithelial–mesenchymal transition-related markers in tumor-bearing mouse model, including TWIST, SLUG, SNAIL, and β-catenin. We observed that β-catenin co-expressed with SLUG and norepinephrine (NE) in tumor tissues obtained from nude mice. Further ex vivo experiments revealed that NE promoted migration and invasion of ovarian cancer cells and SLUG expression through upregulating expression and improving transcriptional function of β-catenin in vitro. A human phosphor-kinase array suggested that NE activated various kinases in ovarian cancer cells, and we further confirmed that AKT inhibitor reduced NE-mediated pro-metastatic impacts and activation of the β-catenin/SLUG axis. Furthermore, the expression levels of NE and β-catenin were examined in ovarian tumor tissues by using tumor tissue arrays. Results showed that the expression levels of both NE and β-catenin were associated with poor clinical stage of serous EOC. Moreover, we found that melatonin (MLT) effectively reduced the abdominal tumor burden of ovarian cancer induced by CRS, which was partially related to the inhibition of the NE/AKT/β-catenin/SLUG axis. Collectively, these findings suggest a novel mechanism for CRS-mediated ovarian cancer metastasis and MLT has a potential therapeutic efficacy against ovarian cancer.

scholarly journals MiRNA-802 suppresses proliferation and migration of epithelial ovarian cancer cells by targeting YWHAZ

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Yang ◽  
Li Sun ◽  
Lei Liang
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Target Genes ◽  
Gene Prediction ◽  
Biological Effects ◽  
Expression Level ◽  
Ovarian Cancer Cells ◽  
And Migration

Abstract Background The imbalance of expression of microRNA-802 may have a significant place in tumor progression. However, the bio-function of epithelial ovarian cancer cells remains unclear. Therefore, we setup this study to explore the pathogenesis of epithelial ovarian cancer based on microRNA-802. Methods RT-qPCR analysis was used to measure the expression level of microRNA802 and YWHAZ in epithelial ovarian cancer. CCK-8, colony formation, flow cytometry and transwell assay were used to detect the effects of microRNA-802 on cell proliferation, apoptosis, invasion and migration. Target gene prediction and screening, luciferase reporting experiments were applied to validate the downstream target genes of microRNA-802. The effects of microRNA-802 on the expression of YWHAZ and its biological effects were measured by Western blotting and RT-qPCR. Results Compared with normal cell lines and tissues, the expression level of microRNA-802 was obviously down-regulated in cancer related cell lines and tissues. Overexpression of microRNA-802 could obviously inhibit the invasion and proliferation and induce apoptosis. In addition, YWHAZ was the binding target protein of miR-802 for epithelial ovarian cancer cells. YWHAZ was obviously up-regulated in human epithelial ovarian cancer cells, and YWHAZ was negatively correlated with the expression of miR-802. YWHAZ can partly eliminate the inhibitory effect caused by overexpression of miR-802 on growth and metastasis of epithelial ovarian cancer cells. Conclusion miR-802 can regulate the occurrence and development of epithelial ovarian cancer by targeting YWHAZ.

scholarly journals circ-CSPP1 promotes proliferation, invasion and migration of ovarian cancer cells by acting as a miR-1236-3p sponge

2019 ◽  
Vol 114 ◽  
pp. 108832 ◽  
Author(s):  
Qian-hui Li ◽  
Yao Liu ◽  
Shuo Chen ◽  
Zhi-hong Zong ◽  
Yu-ping Du ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Invasion And Migration ◽  
And Migration
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