scholarly journals ERRα Expression in Ovarian Cancer and Promotes Ovarian Cancer Cells Migration in Vitro

2021 ◽  
Author(s):  
Weiyi Huang ◽  
Lili Chen ◽  
Pengming Sun
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Expression Level ◽  
Ovarian Cancer Cells ◽  
Low Grade ◽  
Mrna Expression Level ◽  
Invasion And Metastasis ◽  
Cancer Tissues

Abstract Purpose: Ovarian cancer is one of the common gynecological malignancies, which is prone to metastasize and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) is highly expressed in various malignant tumors. Our objective was to explore the impact of ERRα expression on the progression of ovarian cancer. Methods: The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western Blot methods. The cellular ERRα expression was up-regulated via lentivirus transfection and down-regulated via specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were observed by wound healing assay and trans-well chamber assay. Results: The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues compared with those in early-stage and low-grade tissues. Ovarian cancer cells with higher expression level of ERRα had stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, there was a positive correlation between the percentages of wound closure and cellular ERRα mRNA expression level (r=0.921, P<0.01), and the cell invasiveness was also positively correlated with the cellular ERRα mRNA expression level (r=0.926, P<0.01). Conclusions: Our results suggest that ERRα may play a positive role in the progression of ovarian cancer, and may serve as a promising predictive biomarker.

scholarly journals Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1028
Author(s):  
Nikolaos Nikoleousakos ◽  
Panagiotis Dalezis ◽  
Aikaterini Polonifi ◽  
Elena G. Geromichalou ◽  
Sofia Sagredou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Lines ◽  
Synthetic Lethality ◽  
Parp Inhibitor ◽  
Positive Control ◽  
Ovarian Cancer Cells ◽  
Antitumor Effects

We evaluated three newly synthesized B-lactam hybrid homo-aza-steroidal alkylators (ASA-A, ASA-B and ASA-C) for their PARP1/2 inhibition activity and their DNA damaging effect against human ovarian carcinoma cells. These agents are conjugated with an alkylating component (POPA), which also served as a reference molecule (positive control), and were tested against four human ovarian cell lines in vitro (UWB1.289 + BRCA1, UWB1.289, SKOV-3 and OVCAR-3). The studied compounds were thereafter compared to 3-AB, a known PARP inhibitor, as well as to Olaparib, a standard third-generation PARP inhibitor, on a PARP assay investigating their inhibitory potential. Finally, a PARP1 and PARP2 mRNA expression analysis by qRT-PCR was produced in order to measure the absolute and the relative gene expression (in mRNA transcripts) between treated and untreated cells. All the investigated hybrid steroid alkylators and POPA decreased in vitro cell growth differentially, according to the sensitivity and different gene characteristics of each cell line, while ASA-A and ASA-B presented the most significant anticancer activity. Both these compounds induced PARP1/2 enzyme inhibition, DNA damage (alkylation) and upregulation of PARP mRNA expression, for all tested cell lines. However, ASA-C underperformed on average in the above tasks, while the compound ASA-B induced synthetic lethality effects on the ovarian cancer cells. Nevertheless, the overall outcome, leading to a drug-like potential, provides strong evidence toward further evaluation.

scholarly journals Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769430 ◽  
Author(s):  
Zhenhua Du ◽  
Xianqun Sha
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Natural Form ◽  
Ovarian Cancer Cell Lines ◽  
Induced Apoptosis ◽  
Tumor Suppressive Function ◽  
Cancer Tissues

Curcumin is a natural agent that has ability to dampen tumor cells’ growth. However, the natural form of curcumin is prone to degrade and unstable in vitro. Here, we demonstrated that demethoxycurcumin (a curcumin-related demethoxy compound) could inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Moreover, IRS2/PI3K/Akt axis was inactivated in cells treated with demethoxycurcumin. Quantitative real-time reverse transcription polymerase chain reaction demonstrated that miR-551a was down-regulated in ovarian cancer tissues and ovarian cancer cell lines. Over-expression of miR-551a inhibited cell proliferation and induced apoptosis of ovarian cancer cells, whereas down-regulation of miR-551a exerted the opposite function. Luciferase assays confirmed that there was a binding site of miR-551a in IRS2, and we found that miR-551a exerted tumor-suppressive function by targeting IRS2 in ovarian cancer cells. Remarkably, miR-551a was up-regulated in the cells treated with demethoxycurcumin, and demethoxycurcumin suppressed IRS2 by restoration of miR-551a. In conclusion, demethoxycurcumin hindered ovarian cancer cells’ malignant progress via up-regulating miR-551a.

Critical role of SEMA5A expression in invasion and metastasis of ovarian cancer cell

2014 ◽  
Vol 2 (4) ◽  
pp. 247-259
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Critical Role ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Invasion And Metastasis

Semaphorins are a large family of genes involved in the development and morphogenesis of the nervous system. SEMA5A has been reported as a bi-functional molecule, acting as both oncogene and tumor suppressor in different types of cancer. High expression levels of SEMA5A and its receptor, Plexin-B3, were associated with aggressiveness in pancreatic and prostate cancers. Our previous study in ovarian cancer metastasis indicates that FAK knock-down can suppress ovarian cancer cells migration and invasion. We hypothesized that SEMA5A expression promotes ovarian cancer invasion and metastasis. We investigated the expression of SEMA5A in patients with metastatic ovarian cancer (n = 43), localized tumor (n = 37) and normal ovarian tissue (n = 12) from non-malignant diseases as control with different histopathological characteristics. For Silencing of SEMA5A in vitro, we treated human ovarian cancer cells (OVCAR-3, A2780/CP70) with miR-27a and miR-27b. We observed significantly higher expression of SEMA5A protein (P= 0.001) in metastatic ovarian cancer tissue associated with poor overall survival outcomes compared to localized ovarian cancer and control. In vitro silencing of SEMA5A reduced migration and invasion of ovarian cancer cell. Our data offer opportunities for the therapeutic modulation and biomarker of metastatic ovarian cancer.

Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways

2012 ◽  
Vol 442 (2) ◽  
pp. 293-302 ◽  
Author(s):  
Ming-Cheng Chang ◽  
Chi-An Chen ◽  
Pao-Jen Chen ◽  
Ying-Cheng Chiang ◽  
Yu-Li Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Tumour Progression ◽  
Cancer Invasion ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cancer Tissues ◽  
Specific Inhibitors

Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2- or JNK-specific inhibitors, or a decoy AP-1 (activator protein 1) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer.

BRCA1 as a predictive marker of survival in sporadic ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5512-5512
Author(s):  
C. R. James ◽  
J. E. Quinn ◽  
P. B. Mullan ◽  
P. G. Johnston ◽  
D. P. Harkin
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Predictive Marker ◽  
Ovarian Cancer Cells ◽  
Brca1 Expression ◽  
Response To Chemotherapy ◽  
Ovarian Tumours ◽  
Brca1 Mrna

5512 Background: First line treatment of ovarian cancer (OC) involves both Platinum and Taxane based chemotherapy and reduced BRCA1 mRNA and protein expression levels are observed in up to 70% of sporadic ovarian tumours. We, therefore, investigated whether BRCA1 may represent a biomarker of response to chemotherapy in sporadic ovarian cancer. Methods: As in vitro models of sporadic ovarian cancer, we used both antisense and siRNA to abrogate BRCA1 expression in BG-1 and OVCAR5 ovarian cancer cells, respectively. Apoptotic responses to DNA damaging agents and antimicrotubule agents were measured using dose inhibition assays and Annexin V flow cytometry. Quantitiative real time PCR analysis (qRTPCR) was employed to measure BRCA1 mRNA expression in 54 surgically resected ovarian tumours. Univariate analysis provided an evaluation of the effect of BRCA1 mRNA expression and response to platinum or platinum/Taxane containing chemotherapy. Results: We provide in vitro evidence that BRCA1 differentially modulates chemosensitivity in sporadic ovarian cancer. Specifically, we demonstrate that antisense and siRNA inhibition of BRCA1 expression in both BG1 and OVCAR5 ovarian cancer cells, respectively, results in increased sensitivity to both cisplatin and carboplatin and decreased apoptotic response to both paclitaxel and docetaxel. Subsequently, by retrospective clinical analysis of 54 fresh frozen sporadic ovarian tumours we demonstrate that patients with low levels of BRCA1 have a significantly improved overall survival when treated with a platinum based chemotherapy regimen in comparison to patients with high levels of BRCA1 (30.4 months vs 21 months, p=0.047, HR 0.5). In addition, overall median survival for high BRCA1 expressing patients was found to double upon the addition of a taxane containing regimen (46.82 months vs 21 months, p=0.068, HR 0.44). Conclusions: We demonstrate both in vitro and in vivo evidence to support a role for BRCA1 as a predictive marker of response to chemotherapy in sporadic ovarian cancer. We believe that this study is significant given the high incidence of reduced BRCA1 mRNA and protein levels observed in sporadic ovarian cancer and may therefore have implications for the future management of this disease. No significant financial relationships to disclose.

scholarly journals Forkhead Box Protein C2 (FOXC2) Promotes the Resistance of Human Ovarian Cancer Cells to Cisplatin In Vitro and In Vivo

2016 ◽  
Vol 39 (1) ◽  
pp. 242-252 ◽  
Author(s):  
Chanjuan Li ◽  
Hongjuan Ding ◽  
Jing Tian ◽  
Lili Wu ◽  
Yun Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Mapk Signaling ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Tissues ◽  
Mapk Signaling Pathways

Background/Aims: FOXC2 has been reported to play a role in tumor progression, but the correlations of FOXC2 with the cisplatin (CDDP) resistance of ovarian cancer cells are still unclear. The purpose of the present study is to investigate the roles of FOXC2 in the CDDP resistance of ovarian cancer cells and its possible mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of FOXC2 mRNA in CDDP-resistant or sensitive ovarian cancer tissues and cell lines (SKOV3/CDDP and SKOV3). Gain- and loss-of-function assays were performed to analyze the effects of FOXC2 knockdown or overexpression on the in vitro and in vivo sensitivity of ovarian cancer cells to CDDP and its possible molecular mechanisms. Results: The relative expression level of FOXC2 mRNA in CDDP-resistant ovarian cancer tissues was higher than that in CDDP-sensitive tissues. Also, the expression of FOXC2 mRNA and protein in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) cell line was higher than that in its parental cell line (SOKV3). Small hairpin RNA (shRNA)-mediated FOXC2 knockdown significantly increased the in vitro and in vive sensitivity of SKOV3/CDDP cells to CDDP by enhancing apoptosis, while upregulation of FOXC2 significantly decreased the in vitro and in vivo sensitivity of SKOV3 cells to CDDP by reducing apoptosis. Furthermore, FOXC2 activates the Akt and MAPK signaling pathways, and then induced the decreased expression of Bcl-2 protein and the increased expression of Bax and cleaved caspase-3 proteins. Conclusions: FOXC2 mediates the CDDP resistance of ovarian cancer cells by activation of the Akt and MAPK signaling pathways, and may be a potential novel therapeutic target for overcoming CDDP resistance in human ovarian cancer.

scholarly journals ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer

2020 ◽  
Author(s):  
hanwei cui ◽  
Qian Yi ◽  
Min Tian ◽  
Yuteng Liang ◽  
Jie Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Pathway Activation ◽  
Rna Immunoprecipitation ◽  
Cancer Tissues

Abstract BackgroundAdenosine (A)-to-inosine (I) RNA editing is the most prevalent RNA editing mechanism, in which adenosine deaminases acting on RNA 1 (ADAR1) is a major adenosine deaminase. Increasing evidence suggests that editing dysregulation of ADAR1 plays an important role in human tumorigenesis, while the underlying mechanism remains elusive. MethodsThe clinical relevance of ADAR1 was analyzed by real-time PCR, western blotting and immunohistochemistry of ovarian cancer tissues. ADAR1 function on ovarian cancer cells in vitro were explored by colony formation assay, transwell assay and Brdu-based cell cycle assay in vitro and xenograft models in vivo. Western blotting, immunostaining and DNA/RNA immunoprecipitation-qPCR were conducted to confirm DNA damage and R-loop accumulation in ovarian cancer cells. Co-immunoprecipitation and DNA/RNA immunoprecipitation were performed to detect interaction of DHX9, ADAR1 and R-loop complex in ovarian cancer cells.ResultsWe demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients. Importantly, silence of ADAR1 repressed ovarian cancer cell growth and colony formation in vitro and inhibited ovarian cancer cell tumorigenesis in vivo. Further cell cycle and transcriptome profile analysis revealed that silence of ADAR1 in ovarian cancer cells induced cell cycle arrest at G1/G0 stage. Mechanically, loss of ADAR1 caused R-loop abnormal accumulation, thereby contributing to single stand DNA break and ATR pathway activation. Additionally, ADAR1 interacted with DHX9 to regulate R-loop complex formation, and A-to-I editing of nascent RNA repressed R-loop formation during co-transcriptional process. ConclusionsOur results identify a novel ADAR1/R-loop/ATR axis critical for ovarian cancer progression and a potential target for ovarian cancer therapy.

Biopsy for custom-made treatment: mRNA expression level of cancer-critical genes from gastric/colorectal cancer tissues obtained by endoscopic biopsy.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 33-33 ◽  
Author(s):  
Kazuhiko Tamura ◽  
Takafumi Watanabe ◽  
Masanobu Enomoto ◽  
Hideo Sudou ◽  
Jiro Ogata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Endoscopic Biopsy ◽  
Expression Level ◽  
Strong Correlations ◽  
Mrna Expression Level ◽  
Custom Made ◽  
Primary Focus ◽  
Cancer Tissues

33 Background: In this study, we measured the mRNA expression level of cancer-critical genes from the gastric/colorectal cancer tissues obtained through endoscopic biopsy before treatments and compared its consistency with the sample tissues surgically resected from identical cases. Methods: The study was made on 13 gastric and 19 colorectal cancer cases with patients’ consent. We picked identical cases and measured mRNA expression levels from the tissues endoscopically taken before treatment and the surgically resected ones. For the measurement, DNP (DanenbergTumorProfile) method was used. Examination items are as follows: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR, and VEGF. Results: Upon comparing the consistency between endoscopically sampled biopsy tissues and surgically taken tissues from identical cases, it was found that eight out of ten items showed strong correlations in colorectal cancer cases. The results are as follows: FPGS(r=0.91, p<0.001); GGH(r=0.87, p<0.001); EGFR(r=0.86, p<0.001); Topo I (r=0.81, p<0.001); TS(r=0.79, p<0.001); DHFR(r=0.70, p<0.01); VEGF(r=0.67, p<0.01); and TP(r=0.62, p<0.05). In case of gastric cancers, strong correlations were found in three out of ten items with the following results: EGFR (r=0.98, p<0.001); TS (r=0.91, p<0.001; and DPD (r=0.74, p<0.05). Conclusions: Today’s progresses of preoperative chemotherapy and radiotherapy and developments of endoscopic and surgical treatments allow diverse options for treatments. In such circumstances, the significance of knowing the expression of cancer-critical genes between individuals before treatment in conducting custom-made treatment is profound. There are two issues in applying the expression of cancer-critical genes found through endoscopic biopsy: one is whether enough cancer cells can be obtained through biopsy, and the other is whether the sampled cancer cells reflect the characteristics of primary focus. While there remain issues to be addressed, certain results were achieved in this study. Currently, we are working on accumulating cases to compare them and find out whether the results can be applied to custom-made treatments.

scholarly journals RETRACTED ARTICLE: Long noncoding RNA MLK7-AS1 promotes ovarian cancer cells progression by modulating miR-375/YAP1 axis

2018 ◽  
Vol 37 (1) ◽  
Author(s):  
Huan Yan ◽  
Hong Li ◽  
Pengyun Li ◽  
Xia Li ◽  
Jianjian Lin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Wound Healing ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colony Formation ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Tissues

Abstract Background Long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human ovarian cancer and associated with the proliferation and metastasis of cancer cells. The objective of this study was to investigate the role and the underlying mechanisms of LncRNA MAP3K20 antisense RNA 1 (MLK7-AS1) in ovarian cancer. Methods The expression level of MLK7-AS1 was investigated in human ovarian cancer tissues and cell lines. The effects of MLK7-AS1 knockdown on ovarian cancer cell proliferation, migration, invasion and apoptosis were evaluated in vitro using MTT, colony formation assays, wound healing assays, transwell assays and flow cytometry. Furthermore, the in vivo effects were determined using the immunodeficient NSG female mice. Luciferase reporter assays were employed to identify interactions among MLK7-AS1 and its target genes. Results In the current study, MLK7-AS1 was specifically upregulated in ovarian cancer tissues and cell lines. Knockdown of MLK7-AS1 inhibited the ability of cell migration, invasion, proliferation, colony formation and wound healing, whereas promoted cell apoptosis in vitro. By using online tools and mechanistic analysis, we demonstrated that MLK7-AS1 could directly bind to miR-375 and downregulate its expression. Besides, MLK7-AS1 reversed the inhibitory effect of miR-375 on the growth of ovarian cancer cells, which might be involved in the upregulation of Yes-associated protein 1 (YAP1) expression. Moreover, knockdown MLK7-AS1 expression inhibited primary tumor growth in ovary and metastatic tumors in multiple peritoneal organs including liver and spleen in vivo, which were partly abolished by miR-375 inhibition. Mechanically, we found that MLK7-AS1 modulated the epithelial-mesenchymal transition (EMT) process by interacting with miR-375/YAP1 both in vivo and vitro, which promoted the expression of Slug. Conclusions Taken together, our study showed for the first time that MLK7-AS1 interacted with miR-375 to promote proliferation, metastasis, and EMT process in ovarian cancer cells through upregulating YAP1.

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects
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