scholarly journals H3K27ac-induced lncRNA PAXIP1-AS1 exhibits oncogenic property in ovarian cancer by targeting miR-6744-5p/PCBP2 axis

2020 ◽  
Author(s):  
Yimin Ma ◽  
Wei Zheng
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Bioinformatic Analysis ◽  
Tumor Promoter ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Insight Into ◽  
Oncogenic Property

Abstract We aimed to explore role of lncRNA PAX-interacting protein 1- antisense RNA1(PAXIP1-AS1) in ovarian cancer (OC). RT-qPCR analysis identified upregulation of PAXIP1-AS1 in OC cell lines. Functionally, PAXIP1-AS1 knockdown inhibited cell proliferation, accelerated cell apoptosis, and suppressed cell migration and epithelial-mesenchymal transition (EMT) process. Upregulation PAXIP1-AS1 was induced by CBP-mediated H3K27 acetylation (H3K27ac) via bioinformatic analysis and ChIP assay. Furthermore, PAXIP1-AS1 served as a competing endogenous RNA (ceRNA) to regulate PCBP2 expression by sponging microRNA-6744-5p (miR-6744-5p). Restoration experiments showed that overexpressed PCBP2 rescued effect of silenced PAXIP1-AS1 on cell proliferation, apoptosis, migration and EMT. Overall, lncRNA PAXIP1-AS1 activated by H3K27ac functioned as a tumor promoter in OC via mediating miR-6744-5p/PCBP2 axis, which provided promising insight into exploration on OC therapy.

scholarly journals H3K27ac-induced lncRNA PAXIP1-AS1 promotes cell proliferation, migration, EMT and apoptosis in ovarian cancer by targeting miR-6744-5p/PCBP2 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yimin Ma ◽  
Wei Zheng
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Bioinformatic Analysis ◽  
Tumor Promoter ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Qpcr Analysis ◽  
Insight Into

AbstractWe aimed to explore role of lncRNA PAX-interacting protein 1-antisense RNA1 (PAXIP1-AS1) in ovarian cancer (OC). RT-qPCR analysis identified upregulation of PAXIP1-AS1 in OC cell lines. Functionally, PAXIP1-AS1 knockdown inhibited cell proliferation, accelerated cell apoptosis, and suppressed cell migration and epithelial-mesenchymal transition (EMT) process. Upregulation of PAXIP1-AS1 was induced by CBP-mediated H3K27 acetylation (H3K27ac) via bioinformatic analysis and ChIP assay. Furthermore, PAXIP1-AS1 served as a competing endogenous RNA (ceRNA) to regulate PCBP2 expression by sponging microRNA-6744-5p (miR-6744-5p). Restoration experiments showed that overexpressed PCBP2 rescued effects of silenced PAXIP1-AS1 on cell proliferation, apoptosis, migration and EMT. Overall, lncRNA PAXIP1-AS1 activated by H3K27ac functioned as a tumor promoter in OC via mediating miR-6744-5p/PCBP2 axis, which provided promising insight into exploration on OC therapy.

scholarly journals Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules

2020 ◽  
Vol 21 (8) ◽  
pp. 2934 ◽  
Author(s):  
Magdalena Surman ◽  
Sylwia Kędracka-Krok ◽  
Dorota Hoja-Łukowicz ◽  
Urszula Jankowska ◽  
Anna Drożdż ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Content ◽  
Cell Lines ◽  
Cutaneous Melanoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Starting Point ◽  
Novel Biomarkers

Cutaneous melanoma (CM) is an aggressive type of skin cancer for which effective biomarkers are still needed. Recently, the protein content of extracellular vesicles (ectosomes and exosomes) became increasingly investigated in terms of its functional role in CM and as a source of novel biomarkers; however, the data concerning the proteome of CM-derived ectosomes is very limited. We used the shotgun nanoLC–MS/MS approach to the profile protein content of ectosomes from primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) CM cell lines. Additionally, the effect exerted by CM ectosomes on recipient cells was assessed in terms of cell proliferation (Alamar Blue assay) and migratory properties (wound healing assay). All cell lines secreted heterogeneous populations of ectosomes enriched in the common set of proteins. A total of 1507 unique proteins were identified, with many of them involved in cancer cell proliferation, migration, escape from apoptosis, epithelial–mesenchymal transition and angiogenesis. Isolated ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of different cancer-promoting molecules. Taken together, these results confirm the significant role of ectosomes in several biological processes leading to CM development and progression, and might be used as a starting point for further studies exploring their diagnostic and prognostic potential.

scholarly journals Comprehensive Analysis of The Significance of Hypoxia-Related Genes in Ovarian Cancer

2021 ◽  
Author(s):  
Wancheng Zhao ◽  
Lili Yin
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Principal Component ◽  
Vital Role ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Mesenchymal Transition ◽  
Cancer Genome Atlas ◽  
Pca Algorithm

Abstract Background: Hypoxia-related genes have been reported to play important roles in a variety of cancers. However, their roles in ovarian cancer (OC) have remained unknown. The aim of our research was to explore the significance of hypoxia-related genes in OC patients.Methods: In this study, 15 hypoxia-related genes were screened from The Cancer Genome Atlas (TCGA) database to group the ovarian cancer patients using the consensus clustering method. Principal component analysis (PCA) was performed to calculate the hypoxia score for each patient to quantify the hypoxic status. Results: The OC patients from TCGA-OV dataset were divided into two distinct hypoxia statuses (cluster.A and cluster.B) based on the expression level of the 15 hypoxia-related genes. Most hypoxia-related genes were expressed more highly in the cluster.A group than in the cluster.B group. We also found that patients in the cluster.A group exhibited higher expression of immune checkpoint-related genes, epithelial-mesenchymal transition-related genes, and immune activation-related genes, as well as elevated immune infiltrates. PCA algorithm indicated that patients in the cluster.A group had higher hypoxia scores than that in in the cluster.B group.Conclusions: In summary, our research elucidated the vital role of hypoxia-related genes in immune infiltrates of OC. Our investigation of hypoxic status may be able to improve the efficacy of immunotherapy for OC.

scholarly journals New Actors Driving the Epithelial–Mesenchymal Transition in Cancer: The Role of Leptin

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1676
Author(s):  
Monserrat Olea-Flores ◽  
Juan C. Juárez-Cruz ◽  
Miriam D. Zuñiga-Eulogio ◽  
Erika Acosta ◽  
Eduardo García-Rodríguez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Patients With Cancer

Leptin is a hormone secreted mainly by adipocytes; physiologically, it participates in the control of appetite and energy expenditure. However, it has also been linked to tumor progression in different epithelial cancers. In this review, we describe the effect of leptin on epithelial–mesenchymal transition (EMT) markers in different study models, including in vitro, in vivo, and patient studies and in various types of cancer, including breast, prostate, lung, and ovarian cancer. The different studies report that leptin promotes the expression of mesenchymal markers and a decrease in epithelial markers, in addition to promoting EMT-related processes such as cell migration and invasion and poor prognosis in patients with cancer. Finally, we report that leptin has the greatest biological relevance in EMT and tumor progression in breast, lung, prostate, esophageal, and ovarian cancer. This relationship could be due to the key role played by the enriched tumor microenvironment in adipose tissue. Together, these findings demonstrate that leptin is a key biomolecule that drives EMT and metastasis in cancer.

Complement Component 3 (C3) Is a Mediator of Epithelial-Mesenchymal Transition (EMT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1421-1421
Author(s):  
Min Soon Cho ◽  
Qianghua Hu ◽  
Rajesha Rupaimoole ◽  
Anil Sood ◽  
Vahid Afshar-Kharghan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Mouse Embryos ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract We have shown that complement component 3 (C3) is expressed in malignant ovarian epithelial cells and enhances cell proliferation in vitro and tumor growth in vivo. C3 is secreted by cancer cells into the tumor microenvironment and promotes tumor growth through an autocrine loop. To understand the mechanism of upregulation of C3 expression in malignant epithelial cells, we studied the transcriptional regulation of C3, and found that TWIST1, a major regulator of EMT, binds to the C3 promoter and regulates C3 transcription. Knockdown of the TWIST1 gene reduced C3 mRNA, and TWIST1 overexpression increased C3 mRNA. TWIST1 promotes epithelial-mesenchymal transition (EMT) during normal development and in metastasis of malignant tumors. An important marker of EMT is a reduction in the surface expression of E-cadherin on cells facilitating migration and invasion of these cells. TWIST1 is a transcriptional repressor of E-cadherin; and because TWIST1 increases C3 expression, we investigated whether C3 is also a negative regulator of E-cadherin expression. We overexpressed C3 in ovarian cancer cells by stable transduction of lentivirus carrying C3 cDNA. Overexpression of C3 was associated with 32% reduction in the expression of E-cadherin resulting in enhanced migration ability of cells by 2.3 folds and invasiveness by 1.75 folds, as compared to control cells transduced with control lentivirus. To investigate whether TWIST1-induced reduction in E-cadherin is C3-mediated or not, we studied the effect of TWIST1 overexpression simultaneous with C3 knockdown in ovarian cancer cells. Overexpression of TWIST1 alone resulted in 70% reduction in E-cadherin mRNA and this was completely reversed after simultaneous C3 knockdown in these cells. To investigate the correlation between C3 and TWIST1 in vivo, we studied the co-expression of these two proteins in mouse embryos (physiologic EMT) and in malignant tumors (pathologic EMT). Given the role of EMT in embryogenesis we immunostained mouse embryos at different stages of development, using antibodies against TWIST1 or C3. Transverse section of 9.5-day post-coitum (9.5dpc) mouse embryos showed co-expression of TWIST1 and C3 in otocyst (ot) and hindbrain (hb) of neural crest. In the whole-mounted 11.5dpc mouse embryos, C3 and TWIST1 were co-expressed in limb buds. Given the role of EMT in malignancy, tumors induced in mice after intraperitoneal injection of murine ovarian cancer cells were resected and immunostained for C3 and TWIST1 proteins. TWIST1 and C3 co-localized at tumor edges, where EMT and tumor cells migration occur. Taken together, these data provide evidence that TWIST1 regulates C3 expression, and C3 promotes EMT through E-cadherin. Disclosures No relevant conflicts of interest to declare.

scholarly journals MicroRNA-30 inhibits the growth of human ovarian cancer cells by suppressing RAB32 expression

2022 ◽  
Vol 36 ◽  
pp. 205873842110586
Author(s):  
Yan Zhang ◽  
Min Zhou ◽  
Kun Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Transcriptional Level ◽  
Human Ovarian Cancer ◽  
Mesenchymal Transition

Introduction MicroRNAs (miRs) exhibit the potential to act as therapeutic targets for the management of human cancers including ovarian cancer. The role of microRNA-30 (miR-30) via modulation of RAB32 expression has not been studied in ovarian cancer. Consistently, the present study was designed to characterize the molecular role of miR-30/RAB32 axis in human ovarian cancer. Methods Cell viability was determined by MTT assay. Expression analysis was carried out by qRT-PCR. Dual luciferase assay was used to confirm the interaction between miR-30 and RAB32. Scratch-heal and transwell chamber assays were used to monitor the cell migration and invasion. Western blotting and immunofluorescence assays were used to determine the protein expression. Results The results revealed significant ( p < 0.05) downregulation of miR-30 in human ovarian cancer cell lines. Overexpression of miR-30 in ovarian SK-OV-3 and A2780 cancer cells significantly ( p < 0.05) inhibited their proliferation. Besides, ovarian cancer cells overexpressing miR-30 showed significantly ( p < 0.05) lower migration and invasion. The miR-30 upregulation also altered the expression pattern of marker proteins of epithelial–mesenchymal transition in ovarian cancer cells. In silico analysis predicted RAB32 as the molecular target of miR-30 at post-transcriptional level. The silencing of RAB32 mimicked the tumor-suppressive effects of miR-30 overexpression in ovarian cancer cells. Nonetheless, overexpression of RAB32 could prevent the tumor-suppressive effects of miR-30 on SK-OV-3 and A2780 cancer cells. Conclusion Taken together, the results suggest the tumor-suppressive role of miR-30 and point towards the therapeutic utility of miR-30/RAB32 molecular axis in the management of ovarian cancer

scholarly journals Inhibited Long Non-Coding RNA OIP5-AS1 Elevated microRNA-92a to Suppress Proliferation and Metastasis of Ovarian Cancer Cells by Silencing ITGA6

2020 ◽  
Author(s):  
Yujue Wang ◽  
Lingling Li ◽  
Xun Zhang ◽  
Xiaolan Zhao
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Gene Assay ◽  
Proliferation And Metastasis ◽  
Integrin Alpha 6

Abstract Objective: Over the years, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as essential biomarkers during the development of malignancies. This study was performed to verify the roles of lncRNA opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) and miR-92a in ovarian cancer (OC).Methods: OIP5-AS1, miR-92a and ITGA6 expression in tissues and cells was assessed. The screened OC cells were respectively with integrin alpha 6 (ITGA6)/OIP5-AS1 silenced vector, miR-92a mimic/inhibitor or their negative controls. The viability, migration, invasion and apoptosis of the cells were determined and the levels of epithelial-mesenchymal transition (EMT)-related proteins were also measured. The interactions between OIP5-AS1 and miR-92a, and between miR-92a and ITGA6 were confirmed by dual luciferase report gene assay and/or RNA pull-down assay.Results: OIP5-AS1 and ITGA6 were upregulated while miR-92a was downregulated in OC tissues versus the adjacent normal tissues. Inhibited OIP5-AS1 or elevated miR-92a repressed EMT, viability, migration and invasion of OC cells, and promoted OC cell apoptosis. These effects that induced by silenced OIP5-AS1 could be reversed by miR-92a inhibitor. The reduction of ITGA6 restricted EMT in OC cells. MiR-92a was a target of OIP5-AS1 and ITGA6 was targeted by miR-92a.Conclusion: OIP5-AS1 silencing promoted miR-92a to repress proliferation and metastasis of OC cells through inhibiting ITGA6. This research may provide potential biomarkers for OC.

scholarly journals Role of NELF‑B in supporting epithelial‑mesenchymal transition and cell proliferation during hepatocellular carcinoma progression

2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Mennatallah Ghouraba ◽  
Razan Masad ◽  
Eric Mpingirika ◽  
Omnia Abdelraheem ◽  
Rached Zeghlache ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals LY75 Suppression in Mesenchymal Epithelial Ovarian Cancer Cells Generates a Stable Hybrid EOC Cellular Phenotype, Associated with Enhanced Tumor Initiation, Spreading and Resistance to Treatment in Orthotopic Xenograft Mouse Model

2020 ◽  
Vol 21 (14) ◽  
pp. 4992
Author(s):  
Sadia Mehdi ◽  
Elizabeth Macdonald ◽  
Kristianne Galpin ◽  
David A. Landry ◽  
Galaxia Rodriguez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Severe Combined Immunodeficiency ◽  
Ovarian Cancer Cells ◽  
M Cells ◽  
Mesenchymal Transition ◽  
Resistance To Treatment

The implications of the epithelial–mesenchymal transition (EMT) mechanisms in the initiation and progression of epithelial ovarian cancer (EOC) remain poorly understood. We have previously shown that suppression of the antigen receptor LY75 directs mesenchymal–epithelial transition (MET) in EOC cell lines with the mesenchymal phenotype, associated with the loss of Wnt/β-catenin signaling activity. In the present study, we used the LY75-mediated modulation of EMT in EOC cells as a model in order to investigate in vivo the specific role of EOC cells, with an epithelial (E), mesenchymal (M) or mixed epithelial plus mesenchymal (E+M) phenotype, in EOC initiation, dissemination and treatment response, following intra-bursal (IB) injections of SKOV3-M (control), SKOV3-E (Ly75KD) and a mixed population of SKOV3-E+M cells, into severe combined immunodeficiency (SCID) mice. We found that the IB-injected SKOV3-E cells displayed considerably higher metastatic potential and resistance to treatment as compared to the SKOV3-M cells, due to the acquisition of a Ly75KD-mediated hybrid phenotype and stemness characteristics. We also confirmed in vivo that the LY75 depletion directs suppression of the Wnt/β-catenin pathway in EOC cells, suggestive of a protective role of this pathway in EOC etiology. Moreover, our data raise concerns regarding the use of LY75-targeted vaccines for dendritic-cell EOC immunotherapy, due to the possible occurrence of undesirable side effects.

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