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 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.

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 UBE2C Drives Human Cervical Cancer Progression and Is Positively Modulated by mTOR

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 37
Author(s):  
An-Jen Chiang ◽  
Chia-Jung Li ◽  
Kuan-Hao Tsui ◽  
Chung Chang ◽  
Yuan-chin Ivan Chang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cancer Staging ◽  
Cervical Squamous Cell Carcinoma ◽  
Cancer Cell Proliferation ◽  
Gynecological Malignancy ◽  
In Vivo Experiments ◽  
Ubiquitin Conjugating Enzyme

Cervical cancer is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for cervical cancer has shown unprecedented advantages. Several studies have shown that ubiquitin conjugating enzyme E2 (UBE2C) is highly expressed in a series of tumors, and participates in the progression of these tumors. However, the possible impact of UBE2C on the progression of cervical squamous cell carcinoma (CESC) remains unclear. Here, we carried out tissue microarray analysis of paraffin-embedded tissues from 294 cervical cancer patients with FIGO/TNM cancer staging records. The results indicated that UBE2C was highly expressed in human CESC tissues and its expression was related to the clinical characteristics of CESC patients. Overexpression and knockdown of UBE2C enhanced and reduced cervical cancer cell proliferation, respectively, in vitro. Furthermore, in vivo experiments showed that UBE2C regulated the expression and activity of the mTOR/PI3K/AKT pathway. In summary, we confirmed that UBE2C is involved in the process of CESC and that UBE2C may represent a molecular target for CESC treatment.

scholarly journals Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marina Stasenko ◽  
Evan Smith ◽  
Oladapo Yeku ◽  
Kay J. Park ◽  
Ian Laster ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Therapeutics ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Carbohydrate Binding ◽  
Matrigel Invasion ◽  
Galectin 3

AbstractThe lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti–Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.

scholarly journals HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway

Oncogene ◽  
2021 ◽  
Author(s):  
Yong Wu ◽  
Qinhao Guo ◽  
Xingzhu Ju ◽  
Zhixiang Hu ◽  
Lingfang Xia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Prognostic Indicator ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Proliferation And Metastasis ◽  
Nuclear Ribonucleoprotein

AbstractNumerous studies suggest an important role for copy number alterations (CNAs) in cancer progression. However, CNAs of long intergenic noncoding RNAs (lincRNAs) in ovarian cancer (OC) and their potential functions have not been fully investigated. Here, based on analysis of The Cancer Genome Atlas (TCGA) database, we identified in this study an oncogenic lincRNA termed LINC00662 that exhibited a significant correlation between its CNA and its increased expression. LINC00662 overexpression is highly associated with malignant features in OC patients and is a prognostic indicator. LINC00662 significantly promotes OC cell proliferation and metastasis in vitro and in vivo. Mechanistically, LINC00662 is stabilized by heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1). Moreover, LINC00662 exerts oncogenic effects by interacting with glucose-regulated protein 78 (GRP78) and preventing its ubiquitination in OC cells, leading to activation of the oncogenic p38 MAPK signaling pathway. Taken together, our results define an oncogenic role for LINC00662 in OC progression mediated via GRP78/p38 signaling, with potential implications regarding therapeutic targets for OC.

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.

LncRNA SNHG14 Promotes Progression of Ovarian Cancer by Regulating miR-206 Expression

2021 ◽  
Vol 7 (5) ◽  
pp. 3997-4004
Author(s):  
Zhibo Zou ◽  
Lin Peng
Keyword(s):  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Nude Mice ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Research Objects

Objective: This study aimed to probe into the effect of LncRNA SNHG14 on ovarian cancer progression by regulating miR-206.Methods: Fifty-seven ovarian cancer (OC) patients who were treated in our hospital from December 2017 to December 2019 were collected as the research objects. During the operation, OC tissues and paracancerous tissues of patients were collected, and the effect of SNHG14 on OC tumor growth in nude mice was detected, and SNHG14 inhibitor was transfected into OC cells. The relative expression of SNHG14 in tissues and cells was detected by qRT-PCR, cell proliferation was testedvia CCK8, migration and invasion were detected through Transwell, apoptosis was assessedvia flow cytometry, and the targeted relationship between SNHG14 and miR-206 was detected by dual luciferase reporter gene.Results: SNHG14 is highly expressed in OC tissues, cells and nude mice. Down-regulating it can inhibit the biological ability of OC cells and inhibit the growth of nude mice tumors. It can directly target miR-206 to regulate CCND1 expression and promote OC progression.Conclusion: LncRNA SNHG14 can act as miR-206 sponge to regulate CCND1 expression downstream of miR-206 and promote OC progression.

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 Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
David W. Chan ◽  
Wai-Yip Lam ◽  
Fushun Chen ◽  
Mingo M. H. Yung ◽  
Yau-Sang Chan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Drug Resistance ◽  
Poor Prognosis ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Dna Hypermethylation ◽  
Demethylating Agents ◽  
Ovarian Cancers ◽  
The Impact

Abstract Background In contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC. Methods An epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells. Results Global DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells. Conclusions This study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment. Graphic abstract

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