scholarly journals LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness via Regulating ITGB8

2021 ◽  
Vol 11 ◽  
Author(s):  
Changlei Su ◽  
Kejin Huang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Epithelial Ovarian Cancer ◽  
Figo Stage ◽  
Gynecology And Obstetrics ◽  
Oncogenic Pathways ◽  
Advanced Tumor ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Formation Efficiency

This study aimed to investigate the carcinogenic role of long non-coding RNA T-cell factor 7 (lnc-TCF7) in epithelial ovarian cancer (EOC). Lnc-TCF7 overexpression and shRNA plasmids were transfected into SKOV3 and OVCAR3 cells, followed by measurement of cell proliferation, migration, invasion, apoptosis, stemness, and mRNA profile (via microarray). Besides, lnc-TCF7 expression was measured in tumor and adjacent tissues from 76 EOC patients. Lnc-TCF7 was upregulated in EOC cell lines; its overexpression increased cell proliferation, migration, invasion, but decreased apoptosis and promoted CD44, CD133 expressions, CD44+CD133+ cell proportion, spheres formation efficiency and drug resistance to cisplatin in SKOV3 and OVCAR3 cells. Besides, lnc-TCF7 ShRNA exhibited opposite effects comparing with its overexpression. Microarray analysis revealed 267 mRNAs were modulated by lnc-TCF7 dysregulation, among which ITGB8 was the most dysregulated one, which was validated by subsequent western blot and RT-qPCR. Furthermore, ITGB8 overexpression not only induced proliferation, migration, invasion and stemness, but also attenuated the effect of lnc-TCF7 ShRNA on these functions in SKOV3 and OVCAR3 cells. In addition, lnc-TCF7 was upregulated in tumor tissues and correlated with higher pathological grade, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and worse overall survival in EOC patients. Conclusively, lnc-TCF7 regulates multiple oncogenic pathways, promotes proliferation, migration, invasion, stemness via upregulating ITGB8. It also correlates with advanced tumor features and poor prognosis in EOC, implying its potential as a target for EOC treatment.

scholarly journals Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression

2020 ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

scholarly journals EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhendan Zhao ◽  
Zhiling Wang ◽  
Pengling Wang ◽  
Shujie Liu ◽  
Yingwei Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gynecology And Obstetrics

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

scholarly journals Long Non-coding RNA PTPRG-AS1 Promotes Cell Tumorigenicity in Epithelial Ovarian Cancer by Decoying microRNA-545-3p and Consequently Enhancing HDAC4 Expression

2020 ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also done to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, invasion in vitro, and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. For the mechanism part, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

scholarly journals Long Non-Coding RNA AC022306.2 Promotes Cell Proliferation, Migration, and Invasion by Mediating GALK2 in Epithelial Ovarian Cancer

2021 ◽  
Author(s):  
Xin Liu ◽  
Zhenghao Huang ◽  
Honglei Qin ◽  
Jingwen Chen ◽  
Yang Zhao
Keyword(s):  
Ovarian Cancer ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter System ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Long Non Coding Rna

Abstract BackgroundLong non-coding RNA (LncRNA) has been exhibited to exert significant function among human cancers. AC022306.2, as a newly discovered lncRNA, has an unclear function in ovarian cancer (OC). This study aims to uncover the functional role of AC022306.2 in OC and discover its possible mechanism. MethodsThe expression of AC022306.2 and Galactokinase 2 (GALK2) in OC tissues and adjacent non-tumor tissues was detected via qRT-PCR. The CCK-8 assay, cell clonogenesis assay, scratch healing assay and trans-well assay were used to reveal the function of AC022306.2 and GALK2 in ovarian cancer cell lines. Mice xenografts experiment was performed. Bioinformatics predicted the microRNA (miRNA) that bond with AC022306.2 and GALK2, and dual luciferase reporter system confirmed it. Rescue experiments of miRNA mimics and siGALK2 transfection on the basis of AC022306.2 over-expression were carried out to uncover the mechanism by which AC022306.2 played cancer-promoting roles in ovarian cancer.ResultsIt was found that AC022306.2 was up-regulated in EOC tissues compared with adjacent non-tumor tissues. The elevated expression of AC022306.2 was related to the FIGO stage of OC. Functional experiments showed that AC022306.2 overexpression accelerated proliferation and aggression of OC cells in vitro and accelerated tumor growth in vivo. We also found that GALK2 was up-regulated in OC tissues. The expression of GALK2 mRNA in OC tissue was positively associated with the expression of AC022306.2. After AC022306.2 was knocked down, the expression of GALK2 was down-regulated. In addition, GALK2 depletion restored the proliferation and aggression capabilities of OC cells after AC022306.2 overexpression. Mechanically, AC022306.2 acted as a competitive endogenous RNA (ceRNA) of miR-369-3p to modulate the expression of GALK2. The up-regulating of miR-369-3p or the down-regulating of GALK2 partially reversed the effect of AC022306.2 overexpressed on cell propagation and aggression in OC. ConclusionsAC022306.2 is a new oncogene in the carcinogenesis and development of OC. AC022306.2 improves the development of OC by regulating the miR-369-3p / GALK2 axis, indicating that AC022306.2 may have the potential to become a new molecular target for the treatment of OC.

scholarly journals Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Juanjuan Shi ◽  
Xijian Xu ◽  
Dan Zhang ◽  
Jiuyan Zhang ◽  
Hui Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Ovarian Cancer ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC. Methods Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays. Results Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4. Conclusions PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

Clinical Significance of the Resistance Proteins LRP, Pgp, MRP1, MRP3, and MRP5 in Epithelial Ovarian Cancer

2015 ◽  
Vol 25 (2) ◽  
pp. 236-243 ◽  
Author(s):  
Iva Sedláková ◽  
Jan Laco ◽  
Katerina Caltová ◽  
Miroslav Cervinka ◽  
Jindrich Tošner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcome ◽  
Confidence Interval ◽  
Epithelial Ovarian Cancer ◽  
Figo Stage ◽  
Histological Type ◽  
Rank Test ◽  
Log Rank Test ◽  
Gynecology And Obstetrics ◽  
Mrp1 Expression

ObjectiveThis study aimed to evaluate the correlation between the expressions of lung resistance protein (LRP), P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP)-1, MRP3, and MRP5 and histopathological parameters and clinical outcome, and to determine the predictive and prognostic value of these transport proteins in patients with ovarian cancer.MethodsTumor samples from 111 chemonaive patients with epithelial ovarian cancer who underwent primary surgery from 2006 to 2010 were immunohistochemically stained for LRP, Pgp, MRP1, MRP3, and MRP5 expressions.ResultsMRP1 expression was greater among patients with late disease than among patients with early stage ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) I + II, 71.6% (confidence interval, 60–100); FIGO III + IV, 83.6% (confidence interval, 100–100); P = 0.03]. The histological subtype correlated with the expressions of LRP, Pgp, MRP1, and MRP3. Relapse of disease during the next 24 months occurred more often among patients with higher Pgp and MRP1 than among patients with lower Pgp and MRP1 expressions. FIGO stage, histological type, debulking efficiency, strong Pgp expression, and strong MRP1 expression correlated significantly with shorter progression-free survival (log-rank test, P = 0.001, P = 0.004, P = 0.001, P = 0.051, and P = 0.046, respectively). FIGO stage, histological type, debulking efficiency, and strong MRP1 expression correlated with poor patient survival (log-rank test, P = 0.001, P = 0.042, P = 0.005, and P = 0.018, respectively).ConclusionsPgp and MRP1 expressions were clinically significant in patients with ovarian cancer. Pgp and MRP1 may be reliable, independent predictive and prognostic factors regarding the clinical outcome of ovarian cancer. MRP3 is less important as a predictive and prognostic factor than MRP1 expression. MRP5 and LRP expressions were not applicable prognostic parameters regarding ovarian cancer.

scholarly journals Predictors of Survival Outcomes After Primary Treatment of Epithelial Ovarian Cancer in Lagos, Nigeria

2021 ◽  
pp. 89-98
Author(s):  
Kehinde Sharafadeen Okunade ◽  
Adebola A. Adejimi ◽  
Ephraim O. Ohazurike ◽  
Omolola Salako ◽  
Benedetto Osunwusi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analysis ◽  
Epithelial Ovarian Cancer ◽  
Longitudinal Research ◽  
Menopausal Status ◽  
Figo Stage ◽  
Primary Treatment ◽  
Rank Test ◽  
Gynecology And Obstetrics

PURPOSE This study was designed to investigate the clinicopathologic predictors of progression-free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC) following primary treatment in Lagos, Nigeria. MATERIALS AND METHODS Using data from a retrospective cohort of 126 patients who received treatment for EOC between 2010 and 2018, we identified 83 patients with a complete clinical record for subsequent data analysis. Patients' demographics and updated 2-year follow-up status were abstracted from medical records. Kaplan-Meier survival curves were compared using the log-rank test, and Cox proportional hazard models were used for multivariate analysis to identify independent predictors of survivals following treatment in EOC patients. RESULTS The median PFS and OS were 12 and 24 months, respectively. After adjusting for covariates in the multivariate analysis, younger age ≤ 55 years (hazard ratio [HR] = 0.40; 95% CI, 0.22 to 0.74; P = .01) and International Federation of Gynecology and Obstetrics (FIGO) stage I/II (HR = 0.02; 95% CI, 0.01 to 0.08; P = .01) were independent predictors of improved PFS, whereas being premenopausal (HR = 2.34; 95% CI, 1.16 to 4.75; P = .02) was an independent predictor of reduced OS after 2-year follow-up. CONCLUSION PFS could be predicted by the age and FIGO stage of the disease, whereas menopausal status was predictive of OS in patients with EOC. This knowledge should form the basis for counseling patients with ovarian cancer during their primary treatment and lend support to the importance of aggressive follow-up and monitoring for the older, premenopausal patients and those with an advanced stage of epithelial ovarian cancer. However, robust longitudinal research should be carried out to provide additional reliable insight to this information.

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