Clinical Significance of miR-575 in Ovarian Cancer and Its Effect on Ovarian Cancer Cells

2020 ◽  
Vol 12 (9) ◽  
pp. 1087-1094
Author(s):  
Jie Wang ◽  
Weixin Zhou ◽  
Xilun Gan ◽  
Jianbo Yang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Critical Role ◽  
Protein Detection ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Pten Protein ◽  
Apoptosis Protein ◽  
The Impact ◽  
Proliferation And Invasion

Ovarian cancer (OC) is a common form of gynecological cancer that increases in incidence annually, seriously threatening the health and safety of patients. The critical role of miR-575 in multiple neoplastic diseases has already been well established. We suspected that miRNA-575 may be strongly associated with the occurrence of OC and may be the key to OC diagnosis and treatment in the future. To test this hypothesis, we selected 68 OC patients (research group, or RG) who were admitted to our hospital and 60 concurrent healthy controls (control group, or CG) as the study participants. Human OC cell lines A2780, OVCAR-3, and SK-OV-3, and human normal ovarian epithelial cells IOSE80 were used in this study. Nanoparticle-assisted polymerase chain reaction (Nano-PCR), was used to identify miRNA-575 expression and its diagnostic implications in OC. miRNA-575 expression in OC cells and its influence on OC cell biological behaviors were investigated, and the correlation between miR-575 and the phosphatase and tensin homolog (PTEN) was discussed. The results revealed a highly expressed miRNA-575 in OC. Detection of biological behaviors was conducted after transfection of miRNA-575 into OC cells. Cell proliferation and invasion in the mimics-miRNA-575 group was statistically enhanced compared to the negative control (NC) and ininhibition-miRNA-575 groups, and the apoptosis and apoptosis protein count significantly declined (P < 0.05). Subsequently, PTEN was observed to present a lower expression in OC cells. Online target gene analysis website (http://www.targetscan.org/vert_72/) identified the related sites that could bind miR-575 and PTEN. PTEN protein detection in the mimics-miR-575, ininhibition-miR-575, and NC groups showed that the PTEN protein expression in the mimics-miR-575 group was reduced in comparison with that of the other groups, while that for ininhibition-miR-575 was elevated compared to that of the NC group (P < 0.05). Therefore, we came to the conclusion that a high expression of miR-575 can bolster OC cell proliferation and invasion and inhibit apoptosis, while the impact of miR-575 on OC cells may be achieved via targeting the PTEN protein. miR-575 presents important clinical applications in OC diagnosis as an underlying therapeutic target of OC and is a major breakthrough toward future OC research.

MicroRNA-301a Promotes Cell Proliferation and Resistance to Apoptosis through PTEN/PI3K/Akt Signaling Pathway in Human Ovarian Cancer

2021 ◽  
pp. 1-9
Author(s):  
Jie Ni ◽  
Ying Chen ◽  
Beibei Fei ◽  
Yan Zhu ◽  
Yibei Du ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Critical Role ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Akt Signaling Pathway

Background: MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. Objective: The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. Methods: The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. Results: We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. Conclusion: Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.

scholarly journals Platelet-activating factor acetyl hydrolase IB2 dysregulated cell proliferation in ovarian cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YingYing He ◽  
Zhicheng He ◽  
Xiaoyu Zhang ◽  
Shubai Liu
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Platelet Activating Factor ◽  
Regulatory Subunit ◽  
Ovarian Cancer Cells ◽  
Cancer Tissue ◽  
Serine Esterase ◽  
Cancer Pathogenesis ◽  
The Impact

Abstract Background Ovarian cancer is the leading cause of death from gynaecologic illnessed worldwide. Platelet-activating factor acetyl hydrolase IB2 (PAF-AH IB2) is an intracellular serine esterase that hydrolyzes platelet-activating factor, a G-protein-like trimer with two catalytic subunits and one regulatory subunit. The regulatory role of PAF-AH IB2 in the oncogenesis of ovarian cancer is not well understood. Methods In this study, the TCGA dataset and clinical cancer tissue microarray were utilized to investigate abnormal overexpression of PAF-AH IB2 in ovarian cancer. To investigate the impact on the cell proliferation, migration, and tumorigenicity in vitro, PAF-AH IB2 stable knocking down (KD) ovarian cancer cells were established by ShRNA. The whole transcription profiling, tyrosine kinase profiling and standard cell functional assays were integrated to explore the biological importance and mechanism of PAF-AH IB2 modulated in ovarian cancer. Results PAF-AH IB2 was identified significantly overexpression in four subtypes of ovarian cancer. In vitro, PAF-AH IB2 KD significantly inhibited cancer cell proliferation, migration, and tumorigenicity, activated caspases and caused cell cycle arrest, and made the cells more sensitive to PAF. PAF-AH 1B2 KD cells down-regulated several key regulators of the multiple tyrosine kinases-mediated signaling pathway, suggesting a novel interaction network between the growth factor receptors pathway and PAF-AH 1B2 mediated PAF signalling. Conclusions These findings revealed a previously undiscovered role for PAF-AH IB2 as a potenial therapy target and essential signaling mediators in ovarian cancer pathogenesis, as well as new possible preventive and therapeutic strategies to inhibit this enzyme in clinical treatment for ovarian cancer.

scholarly journals Time-Dependent Effects of POT1 Knockdown on Proliferation, Tumorigenicity, and HDACi Response of SK-OV3 Ovarian Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hua Zhou ◽  
Abdul Mondal ◽  
Aleksandra Dakic ◽  
Lama Alhawas ◽  
Xuefeng Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Telomerase Activity ◽  
Population Doubling ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Activity Levels ◽  
Mrna Levels ◽  
The Impact

The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot. The relative telomerase activity levels were detected using qTRAP; cell proliferation was assessed using cumulative population doubling (cPD) experiments. Cell tumorigenicity was evaluated by anchorage-independent cell growth assays, and cell response to HDACi was determined by luminescence cell viability assays. Results indicate that lenti-shRNA-mediated POT1-KD significantly reduced POT1 mRNA and protein expression. POT1-KD immediately downregulated c-Myc expression, which led to the inhibition of cell proliferation, tumorigenesis, and HDACi response. However, after brief suppression, c-Myc expression increased in the medium term, which resulted in enhanced cell proliferation, tumorigenesis, and HDACi response in the POT1-KD cells. Furthermore, we discovered that c-Myc regulated cell proliferation and tumorigenesis via hTERT/telomerase/telomere pathway.

scholarly journals Hormone response in ovarian cancer: time to reconsider as a clinical target?

2012 ◽  
Vol 19 (6) ◽  
pp. R255-R279 ◽  
Author(s):  
Francesmary Modugno ◽  
Robin Laskey ◽  
Ashlee L Smith ◽  
Courtney L Andersen ◽  
Paul Haluska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Critical Role ◽  
Developed Countries ◽  
Ovarian Cancer Cells ◽  
Small Subset ◽  
Gynecologic Malignancies ◽  
Epidemiological Evidence ◽  
Ovarian Tumorigenesis ◽  
Proliferation And Invasion

Ovarian cancer is the sixth most common cancer worldwide among women in developed countries and the most lethal of all gynecologic malignancies. There is a critical need for the introduction of targeted therapies to improve outcome. Epidemiological evidence suggests a critical role for steroid hormones in ovarian tumorigenesis. There is also increasing evidence fromin vitrostudies that estrogen, progestin, and androgen regulate proliferation and invasion of epithelial ovarian cancer cells. Limited clinical trials have shown modest response rates; however, they have consistently identified a small subset of patients that respond very well to endocrine therapy with few side effects. We propose that it is timely to perform additional well-designed trials that should include biomarkers of response.

scholarly journals CircASH2L Promotes Ovarian Cancer Tumorigenesis, Angiogenesis, and Lymphangiogenesis by Regulating the miR-665/VEGFA Axis as a Competing Endogenous RNA

2020 ◽  
Vol 8 ◽  
Author(s):  
Jinxin Chen ◽  
Xiaocen Li ◽  
Lu Yang ◽  
Mengmeng Li ◽  
Ye Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Western Blots ◽  
The Impact

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. Emerging research has revealed a close relationship between circular RNAs (circRNAs) and ovarian cancer development, metastasis, and prognosis. The objective of our research was to further explore the relationship between circASH2L and ovarian cancer. Quantitative real-time polymerase chain reaction was used to detect the differential expression of circRNAs between normal ovaries and ovarian cancer tissues. The impact of circASH2L on the proliferation, invasion, and tumorigenicity of ovarian cancer cells was evaluated using gain- and loss-of-function experiments. The molecular mechanisms of circASH2L function were investigated using bioinformatics analysis, RNA fluorescence in situ hybridization, western blots, and dual-luciferase reporter assays. The results showed that circASH2L was remarkably upregulated in ovarian cancer. The invasion and growth of ovarian cancer cells were suppressed by circASH2L knockdown in vitro, and downregulation of circASH2L restrained both angiogenesis and lymphangiogenesis of tumor xenografts in vivo. Furthermore, circASH2L was mostly distributed in the cytoplasm, where it competes with vascular endothelial growth factor A (VEGFA) for binding to miR-665. These findings indicate that circASH2L has an oncogenic function in ovarian cancer. In conclusion, circASH2L plays a critical role in regulating ovarian cancer cell tumorigenesis, angiogenesis, and lymphangiogenesis through the miR-665/VEGFA axis and, therefore, is a possible candidate target for ovarian cancer treatment.

scholarly journals BCL7C suppresses ovarian cancer growth by inactivating mutant p53

2020 ◽  
Author(s):  
Canhua Huang ◽  
Qian Hao ◽  
Getao Shi ◽  
Xiang Zhou ◽  
Yu Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Genes ◽  
Ovarian Cancer Cells ◽  
Mutant P53 ◽  
Ovarian Carcinomas ◽  
Ovarian Tumorigenesis ◽  
P53 Target Genes ◽  
Proliferation And Invasion

Abstract B-cell CLL/lymphoma 7 protein family member C (BCL7C) located at chromosome 16p11.2 shares partial sequence homology with the other two family members, BCL7A and BCL7B. Its role in cancer remains completely unknown. Here, we report our finding of its tumor-suppressive role in ovarian cancer. Supporting this is that BCL7C is downregulated in human ovarian carcinomas, and its underexpression is associated with unfavorable prognosis of ovarian cancer as well as some other types of human cancers. Also, ectopic BCL7C restrains cell proliferation and invasion of ovarian cancer cells. Consistently, depletion of BCL7C reduces apoptosis and promotes cell proliferation and invasion of these cancer cells. Mechanistically, BCL7C suppresses mutant p53-mediated gene transcription by binding to mutant p53, while knockdown of BCL7C enhances the expression of mutant p53 target genes in ovarian cancer cells. Primary ovarian carcinomas that sustain low levels of BCL7C often show the elevated expression of mutant p53 target genes. In line with these results, BCL7C abrogates mutant p53-induced cell proliferation and invasion, but had no impact on proliferation and invasion of cancer cells with depleted p53 or harboring wild-type p53. Altogether, our results demonstrate that BCL7C can act as a tumor suppressor to prevent ovarian tumorigenesis and progression by counteracting mutant p53 activity.

scholarly journals Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs

2021 ◽  
Vol 22 (8) ◽  
pp. 4243
Author(s):  
Karolina Wojtowicz ◽  
Karolina Sterzyńska ◽  
Monika Świerczewska ◽  
Michał Nowicki ◽  
Maciej Zabel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Effects ◽  
The Impact

Our goal was to examine the anticancer effects of piperine against the resistant human ovarian cancer cells and to explore the molecular mechanisms responsible for its anticancer effects. Our study used drug-sensitive ovarian cancer cell line W1 and its sublines resistant to paclitaxel (PAC) and topotecan (TOP). We analyzed the cytotoxic effect of piperine and cytostatic drugs using an MTT assay. The impact of piperine on protein expression was determined by immunofluorescence and Western blot. We also examined its effect on cell proliferation and migration. We noticed a different level of piperine resistance between cell lines. Piperine increases the cytotoxic effect of PAC and TOP in drug-resistant cells. We observed an increase in PTPRK expression correlated with decreased pTYR level after piperine treatment and downregulation of P-gp and BCRP expression. We also noted a decrease in COL3A1 and TGFBI expression in investigated cell lines and increased COL3A1 expression in media from W1PR2 cells. The expression of Ki67 protein and cell proliferation rate decreased after piperine treatment. Piperine markedly inhibited W1TR cell migration. Piperine can be considered a potential anticancer agent that can increase chemotherapy effectiveness in cancer patients.

scholarly journals Epigenetic Silencing of miR-33b Promotes Peritoneal Metastases of Ovarian Cancer by Modulating the TAK1/FASN/CPT1A/NF-κB Axis

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4795
Author(s):  
Xueyu Wang ◽  
Mingo M. H. Yung ◽  
Rakesh Sharma ◽  
Fushun Chen ◽  
Ying-Tung Poon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Critical Role ◽  
Peritoneal Metastases ◽  
Epigenetic Silencing ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Epigenetic Alterations ◽  
The Impact

Peritoneal metastases are frequently found in high-grade serous carcinoma (HGSOC) patients and are commonly associated with a poor prognosis. The tumor microenvironment (TME) is a complex milieu that plays a critical role in epigenetic alterations driving tumor development and metastatic progression. However, the impact of epigenetic alterations on metastatic ovarian cancer cells in the harsh peritoneal microenvironment remains incompletely understood. Here, we identified that miR-33b is frequently silenced by promoter hypermethylation in HGSOC cells derived from metastatic omental tumor tissues. Enforced expression of miR-33b abrogates the oncogenic properties of ovarian cancer cells cocultured in omental conditioned medium (OCM), which mimics the ascites microenvironment, and in vivo tumor growth. Of note, restoration of miR-33b inhibited OCM-upregulated de novo lipogenesis and fatty acid β-oxidation in ovarian cancer cells, indicating that miR-33b may play a novel tumor suppressor role in the lipid-mediated oncogenic properties of metastatic ovarian cancer cells found in the omentum. Mechanistic studies demonstrated that miR-33b directly targets transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing the activities of fatty acid synthase (FASN) and carnitine palmitoyltransferase 1A (CPT1A) in modulating lipid metabolic activities and simultaneously inhibiting the phosphorylation of NF-κB signaling to govern the oncogenic behaviors of ovarian cancer cells. Thus, our data suggest that a lipid-rich microenvironment may cause epigenetic silencing of miR-33b, which negatively modulates ovarian cancer peritoneal metastases, at least in part, by suppressing TAK1/FASN/CPT1A/NF-κB signaling.

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