scholarly journals Dynamic changes in the urine proteome in two ovarian cancer rat models

2019 ◽  
Author(s):  
Yuqiu Li ◽  
Linpei Zhang ◽  
Wenshu Meng ◽  
Youhe Gao
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Cancer Progression ◽  
The Body ◽  
Cancer Development ◽  
Ovarian Cancer Cells ◽  
Rat Models ◽  
Gynecological Malignancy ◽  
Injection Model ◽  
Differential Proteins

AbstractOvarian cancer is the most lethal gynecological malignancy in women, and it is likely to metastasize and has a poor prognosis. The early and reliable diagnosis and monitoring of ovarian cancer is very important. Without a homeostasis mechanism, urine can reflect early systemic changes in the body and has a great potential to be used for the early detection of cancer. This study tested whether early changes could be detected in two ovarian cancer rat models. Two rat models were established by either intraperitoneal (i.p.) or orthotopic (o.t.) injection of NuTu-19 ovarian cancer cells in female Fischer344 rats. Urine samples from ovarian cancer rats were collected at five time points during cancer development, and urinary proteins from the rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with pre-injection samples, 49 differential proteins that have human orthologues were significantly changed in the orthotopically injected model. Among them, 24 of the differential proteins have previously been reported to be associated with ovarian cancer, six of which were reported to be biomarkers of ovarian cancer. On the 7th day after orthotopic injection, four differential proteins (APOA1, OX2G, CHMP5, HEXB) were identified before obvious metastases appeared. In the intraperitoneal injection model, 76 differential proteins were changed during the course of ovarian cancer development. The results show that urine proteins could enable the early detection and monitoring of ovarian cancer progression and could lay a foundation for further exploration of the biomarkers of ovarian cancer.

scholarly journals Early Detection Biomarkers for Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Sreeja Sarojini ◽  
Ayala Tamir ◽  
Heejin Lim ◽  
Shihong Li ◽  
Shifang Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Minimally Invasive ◽  
Early Onset ◽  
Cancer Development ◽  
Transvaginal Ultrasonography ◽  
Screening Methods ◽  
Gynecological Malignancy ◽  
Biomarker Analysis ◽  
Current Practices

Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs.

Adipose-derived stem cells in ovarian cancer progression, metastasis, and chemoresistance

2021 ◽  
pp. 153537022110238
Author(s):  
Wenjing Zhang ◽  
Carolina Torres-Rojas ◽  
Junming Yue ◽  
Bing-Mei Zhu
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Early Stage ◽  
Ovarian Cancer Cells ◽  
High Recurrence Rate ◽  
Gynecological Malignancy ◽  
Adipose Derived Stem Cell

Ovarian cancer is the deadliest gynecological malignancy due to its symptomless early stage, metastasis, and high recurrence rate. The tumor microenvironment contributes to the ovarian cancer progression, metastasis, and chemoresistance. Adipose-derived stem cell in the tumor microenvironment of ovarian cancer, as a key player, interacts with ovarian cancer cells to form the cancer-associated fibroblasts and cancer-associated adipocytes, and secretes soluble factors to activate tumor cell signaling, which can promote ovarian cancer metastasis and chemoresistance. We summarize in this review the recent progress in the studies of interactions between adipose-derived stem cell and ovarian cancer, thus, to provide some insight for ovarian cancer therapy through targeting adipose-derived stem cell.

scholarly journals DGAT1 Expression Promotes Ovarian Cancer Progression and Is Associated with Poor Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Leilei Xia ◽  
Ye Wang ◽  
Shengyun Cai ◽  
Mingjuan Xu
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Rapid Development ◽  
Lipid Synthesis ◽  
Cancer Staging ◽  
The Cancer Genome Atlas ◽  
Ovarian Cancer Cells ◽  
Gynecological Malignancy

Background. Ovarian cancer is the most fatal gynecological malignancy. Owing to its insidious onset, rapid development, and poor prognosis, ovarian cancer is the fifth most common cause of death in women. Although immunotherapy-related drugs, such as Olaparib, can alleviate ovarian cancer progression, there are no remarkable breakthroughs for its effective treatment. It is considered that the transformation of normal cells to cancerous ones involves “recoding” of certain metabolic pathways. Diacylglycerol O-acyltransferase 1 (DGAT1) can synthesize triglycerides by transferring acyl-CoA to diacylglycerol, which plays a key role in lipid synthesis. However, the role of DGAT1 in ovarian cancer is not yet elucidated. Materials and Methods. We analyzed the correlation between DGAT1 and ovarian cancer staging, grading, vascular invasion, and prognosis by collating the information of ovarian cancer specimens from The Cancer Genome Atlas (TCGA) database. Furthermore, the effects of DGAT1 expression on proliferation, migration, invasion, and tumor growth were studied using ovarian cancer cell lines. GSEA was used to analyze the KEGG pathways and biological function enriched because of DGAT1 expression in ovarian cancer. Results. The expression of DGAT1 was elevated in advanced ( p = 0.0432 ), poorly differentiated ( p = 0.0148 ), and vascular invaded ( p = 0.0002 ) ovarian cancer specimens. Prognosis among patients with high expression of DGAT1 was poor. After DGAT1 expression was interfered, proliferation, migration, invasion, colony forming, and tumor growth of ovarian cancer cells were inhibited. In addition, GSEA showed that DGAT1 may be involved in the immune process. Conclusion. DGAT1 expression is associated with the clinical phenotype of ovarian cancer. We suggest that DGAT1 has potential implications in the treatment of ovarian cancer.

scholarly journals Effect of the HDAC Inhibitor on Histone Acetylation and Methyltransferases in A2780 Ovarian Cancer Cells

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 456
Author(s):  
Umamaheswari Natarajan ◽  
Thiagarajan Venkatesan ◽  
Appu Rathinavelu
Keyword(s):  
Ovarian Cancer ◽  
Histone Acetylation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Histone Deacetylases ◽  
Dna Methyltransferase ◽  
Positive Impact ◽  
3D Cell Culture ◽  
Ovarian Cancer Cells ◽  
Histone Hyperacetylation

Background andObjective: Epigenetic modifications are believed to play a significant role in the development of cancer progression, growth, differentiation, and cell death. One of the most popular histone deacetylases inhibitors (HDACIs), suberoylanilide hydroxamic acid (SAHA), also known as Vorinostat, can directly activate p21WAF1/CIP1 gene transcription through hyperacetylation of histones by a p53 independent mechanism. In the present investigation, we evaluated the correlation between histone modifications and DNA methyltransferase enzyme levels following SAHA treatments in A2780 ovarian cancer cells. Materials and Methods: Acetylation of histones and methyltransferases levels were analyzed using RT2 profiler PCR array, immunoblotting, and immunofluorescence methods in 2D and 3D cell culture systems. Results: The inhibition of histone deacetylases (HDAC) activities by SAHA can reduce DNA methyl transferases / histone methyl transferases (DNMTs/HMTs) levels through induction of hyperacetylation of histones. Immunofluorescence analysis of cells growing in monolayers and spheroids revealed significant up-regulation of histone acetylation preceding the above-described changes. Conclusions: Our results depict an interesting interplay between histone hyperacetylation and a decrease in methyltransferase levels in ovarian cancer cells, which may have a positive impact on the overall outcomes of cancer treatment.

scholarly journals Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3388
Author(s):  
Mona Alharbi ◽  
Andrew Lai ◽  
Shayna Sharma ◽  
Priyakshi Kalita-de Croft ◽  
Nihar Godbole ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Multiple Reaction Monitoring ◽  
Metabolic Reprogramming ◽  
Ovarian Cancer Cells ◽  
Platinum Resistance ◽  
Target Cells ◽  
Glycolysis Pathway

Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells’ heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1–6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly (p < 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort (n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management.

scholarly journals HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Jie Dong ◽  
Wei Feng ◽  
Yan Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Clinical Problem ◽  
Ovarian Cancer Cells ◽  
Stem Cell Markers ◽  
Gene Target ◽  
Gynecological Malignancy ◽  
Clonogenic Potential ◽  
Resistant Cells

Ovarian cancer is a deadly gynecological malignancy with resistance to cisplatin a major clinical problem. We evaluated a role of long non-coding (lnc) RNA HOTTIP (HOXA transcript at the distal tip) in the cisplatin resistance of ovarian cancer cells, using paired cisplatin sensitive and resistant A2780 cells along with the SK-OV-3 cells. HOTTIP was significantly elevated in cisplatin resistant cells and its silencing reversed the cisplatin resistance of resistant cells. HOTTIP was found to sponge miR-205 and therefore HOTTIP silenced cells had higher levels of miR-205. Downregulation of miR-205 could attenuate HOTTIP-silencing effects whereas miR-205 upregulation in resistant cells was found to re-sensitize cells to cisplatin. HOTTIP silencing also led to reduced NF-κB activation, clonogenic potential and the reduced expression of stem cell markers SOX2, OCT4, and NANOG, an effect that could be attenuated by miR-205. Finally, ZEB2 was identified as the gene target of miR-205, thus completing the elucidation of HOTTIP-miR-205-ZEB2 as the novel axis which is functionally involved in the determination of cisplatin resistance in ovarian cancer cells.

scholarly journals The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Hidenori Machino ◽  
Syuzo Kaneko ◽  
Masaaki Komatsu ◽  
Noriko Ikawa ◽  
Ken Asada ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Metabolic Stress ◽  
Ovarian Cancer Cells ◽  
Hippo Signaling ◽  
High Grade ◽  
Gynecological Malignancy ◽  
Serous Ovarian Carcinoma

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.

scholarly journals FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in Ovarian Cancer Cells

2018 ◽  
Vol 49 (5) ◽  
pp. 1766-1777 ◽  
Author(s):  
Jie Li ◽  
Songlin Zhang ◽  
Meili Pei ◽  
Lei Wu ◽  
Yanli Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Transwell Assay ◽  
Mesenchymal Transition ◽  
Novel Target ◽  
Snail1 Expression

Background/Aims: Epithelial-mesenchymal transition (EMT) is one of the key mechanisms mediating cancer progression. Snail1 has a pivotal role in the regulation of EMT, involving the loss of E-cadherin and concomitant upregulation of vimentin, among other biomarkers. We have found FSCN1 promoted EMT in ovarian cancer cells, but the precise mechanism of FSCN1 in EMT process has not been clearly elucidated. Methods: The levels of FSCN1 and snail1 were determined in epithelial ovarian cancer(EOC) specimen and in ovarian cancer cells by RT-qPCR. The changes of EMT makers and effects on snail1 by FSCN1 were examined by overexpression or depletion of FSCN1 in EOC cells by RT-qPCR and western blotting. The invasiveness of the FSCN1-modified EOC cells was examined in transwell assay. Co-immunoprecipitation (IP) was performed to detect the interaction between snail1 and FSCN1 in EOC cells. Results: We found FSCN1 and snail1 significantly increased in EOC, and especially in EOC with metastasis. FSCN1 was positively correlated with snail1 expression at the cellular/histological levels. Moreover, we further showed that FSCN1 physiologically interacted with and increased the levels of snail1 to promote ovarian cancer cell EMT. Conclusion: FSCN1 promote EMT through snail1 in ovarian cancer cells. FSCN1 is an attractive novel target for inhibiting invasion and metastasis of EOC cells.

Circular RNA hsa_circ_0078607 suppresses ovarian cancer progression by regulating miR-518a-5p/Fas signaling pathway

2020 ◽  
Author(s):  
Nan Zhang ◽  
Yue Jin ◽  
Qiubo Hu ◽  
Shanshan Cheng ◽  
Chao Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Malignant Tumors ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Cancer Pathogenesis ◽  
Direct Target

Abstract Background: Increasing researches have demonstrated the critical functions of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer. In this study, we aim to investigate abnormally expression of hsa_circ_0078607 and the role of hsa_circ_0078607 during ovarian cancer pathogenesis.Methods: RT-PCR were used to detect the expression of circ_0078607 in ovarian cancer tissues. To determine the functional roles of circ_0078607 in ovarian cancer, cell proliferation and cell invasion assays were performed. Bioinformatics and luciferase reporter analysis were used to predict the target of circ_0078607.Results: In the present study, we first found that circ_0078607 was downregulated in ovarian cancer. Forced circ_0078607 expression significantly suppressed proliferation and promotes apoptosis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified that miR-518a-5p as a direct target of circ_0078607, while Fas as a direct target of miR-518a-5p. MiR-518a-5p negatively regulates Fas in ovarian cancer cells, while overexpression of circ_0078607 could increase the expression of Fas inhibited by miR-518a-5p. Furthermore, overexpression of circ_0078607 could inhibit the proliferation and invasion of ovarian cancer cells caused by miR-518a-5p mimic.Conclusion: The results of the present study revealed that circ_0078607 suppresses ovarian cancer progression by sponging oncogenic miR-518a-5p to induce Fas expression, which may provide new therapeutic approach for ovarian cancer.

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