The role of NF-κB pathway in cancer inflammation of esophageal squamous carcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 42-42
Author(s):  
Ching Tzao ◽  
Li-Yuan Cheng ◽  
Chien-Chih Chang ◽  
Guang-Huan Sun
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Lines ◽  
Angiogenic Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
Th2 Cytokines ◽  
M2 Macrophages ◽  
Cancer Inflammation

42 Background: Chronic inflammation plays an important role in tumorigenesis and tumor progression in human cancers. We aim to investigate the role of NF-kB in cancer inflammation of esophageal squamous cell carcinoma (ESCC). Methods: To generate M2-polarized macrophages, cells of human U937 monocyte cell line were treated with phorbol myristate acetate (PMA, 50 ng/ml) for 6 hours, and then cultured with PMA plus Th2 cytokines, IL-4 (20 ng/ml) and IL-13 (20 ng/ml), for another 18 hours. M2 phenotype was verified by flow cytometry and by cytokine profiling using enzyme-linked immunosorbent assay (ELISA). After co-culture with M2 macrophages, transcription nuclear factor-kB (NF-kB) activity was measured using quantitative polymerase chain reaction (Q-PCR), followed by reconfirmation with Western blot analysis for IkBα in KYSE-170 and -510 ESCC cell lines (kindly provided by Dr. Yutaka Shimada at Kyoto University, Japan). A selective inhibitor to NF-kB, Bay11-7082, was used to treat ESCC cell lines co-cultured with M2 macrophages, followed by cell proliferation, migration, invasion assays and vascular endothelial growth factor (VEGF) secretion by ELISA. The effect of Bay11-7082 (5 mg/kg) against growth of ESCC tumor was tested in xenografted tumors. Results: PMA plus Th2 cytokines treatment promoted differentiation of U937 cells into M2 macrophages. When treated with Bay11-7082, proliferation, migration, invasion and induction of VEGF expression was significantly inhibited in M2 macrophage co-cultured ESCC cells with a down-regulation of IkBα expression. Tumor growth was significantly increased in M2 macrophage co-cultured ESCC cells compared to that of the non-co-cultured controls, which was significantly retarded by treatment with Bay11-7082. Conclusions: NF-kB pathway was activated in ESCC cell lines co-cultured with M2 macrophages with an increase in cell proliferation, cell motility and angiogenic factor in vitro and tumor growth in vivo, which were significantly suppressed by a NF-kB inhibitor, Bay11-7082. These results suggest a role of M2 macrophage in promoting aggressiveness of ESCC cells, possibly through an activation of NF-kB pathway that may serve as a potential therapeutic target for ESCC.

492 TUMOR ASSOCIATED MACROPHAGE PROMOTES EPITHELIAL-TO-MESENCHYMAL TRANSITION IN ESOPHAGEAL SQUAMOUS CELL CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Ching Tzao ◽  
Li-Yuan Cheng ◽  
Chien-Chih Chang
Keyword(s):  
Cell Proliferation ◽  
Epithelial To Mesenchymal Transition ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
M2 Macrophage ◽  
Mesenchymal Transition ◽  
Tumor Associated Macrophage ◽  
Cancer Inflammation ◽  
Emt Markers

Abstract   We aimed to investigate the role of tumor associated macrophage (TAM) in epithelial-to-mesenchymal transition (EMT) in esophageal squamous cell cancer (ESCC). Methods Expression of CD68 and EMT markers was determined in resected ESCC tumors by immunohistochemistry with clinicopathologic correlation. M2-polarized macrophages were generated from human U937 cells treated with 50 ng/ml phorbol myristate acetate (PMA) while cultured with PMA plus Th2 cytokines. KYSE-510 ESCC cell was co-cultured with M2 macrophages, followed by determination of expression for EMT markers by Western blot. In situ expression of E-cadherin and vimentin was determined using immunofluorescence staining Cell proliferation, invasion and extracellular matrix (ECM) adhesion assays were performed to determine phenotypic characteristics of cultured ESCC cells. Results High expression of CD68 in resected ESCC correlated with worse survival. In addition, expression of CD68 in resected ESCC tumors correlated positively with expression of Snail and vimentin but inversely with E-cadherin. Compared with KYSE-510 cells cultured alone, those co-cultured with M2 macrophage showed higher expression of snail, vimentin, and fibronectin with a more spindle-shaped morphology, suggesting a mesenchymal differentiation. Further, cell proliferation, invasion and ECM adhesion were significantly more pronounced in M2 macrophage co-cultured ESCC cells. Conclusion EMT markers correlated with the number of TAM within resected ESCC tumors, suggesting an association of cancer inflammation in promoting EMT in ESCC. A link between cancer inflammation mediated by TAM deemed to be supported by increased expression of EMT markers and phenotypic changes related to EMT in ESCC cells co-cultured with M2 macrophage. Our results suggest an important role of TAM in promoting EMT in tumor microenvironment with regards to cancer inflammation in ESCC.

MEKK3 is required for endothelium function but is not essential for tumor growth and angiogenesis

2007 ◽  
Vol 293 (4) ◽  
pp. C1404-C1411 ◽  
Author(s):  
Yong Deng ◽  
Jianhua Yang ◽  
Marya McCarty ◽  
Bing Su
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Critical Role ◽  
Embryonic Stem ◽  
Angiogenic Factor ◽  
Endothelial Cell Proliferation ◽  
Wild Type

Mitogen-activated protein kinase kinase kinase 3 (MEKK3) plays an essential role in embryonic angiogenesis, but its role in tumor growth and angiogenesis is unknown. In this study, we further investigated the role of MEKK3 in embryonic angiogenesis, tumor angiogenesis, and angiogenic factor production. We found that endothelial cells from Mekk3-deficient embryos showed defects in cell proliferation, apoptosis, and interactions with myocardium in the heart. We also found that MEKK3 is required for angiopoietin-1 (Ang1)-induced p38 and ERK5 activation. To study the role of MEKK3 in tumor growth and angiogenesis, we established both wild-type and Mekk3-deficient tumor-like embryonic stem cell lines and transplanted them subcutaneously into nude mice to assess their ability to grow and induce tumor angiogenesis. Mekk3-deficient tumors developed and grew similarly as control Mekk3 wild-type tumors and were also capable of inducing tumor angiogenesis. In addition, we found no differences in the production of VEGF in Mekk3-deficient tumors or embryos. Taken together, our results suggest that MEKK3 plays a critical role in Ang1/Tie2 signaling to control endothelial cell proliferation and survival and is required for endothelial cells to interact with the myocardium during early embryonic development. However, MEKK3 is not essential for tumor growth and angiogenesis.

Platelets/Megakaryocytes Are Critical Regulators of Tumor Progression in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1793-1793
Author(s):  
Satoshi Takagi ◽  
Shokichi Tsukamoto ◽  
Yawara Kawano ◽  
Michele Moschetta ◽  
Yuji Mishima ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Platelet Aggregation ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Tgf Beta

Abstract Platelets play important roles in both physiological and pathological conditions. For instance, platelets may facilitate cancer metastasis by protecting circulating tumor cells (CTCs) from shear stress and immunological assault during their intravascular phase and by supporting CTCs extravasation. Moreover, soluble factors released from activated platelets enhance proliferation and migration of endothelial cells, thereby promoting tumor angiogenesis. Correlations between increased platelet counts and shorter survival time have been described for many solid tumors. However, the role of platelets/megakaryocytes (MKs) in regulating tumor progression and dissemination in Multiple myeloma (MM) has not been previously examined. We measured the platelet aggregation-inducing abilities of MM cell lines and found MM cell lines (MM.1S, OPM-2, KMS-11, U266, and H929) induced platelet aggregation. This was not observed using leukemia cells (K562) and primary healthy donor-derived peripheral blood mononuclear cells. We next investigated whether platelets interact with MM cells within the bone marrow (BM) niche, in vivo. In order to identify platelets/MKs, femurs were harvested from MM.1S GFP+-harboring mice and stained with a DyLight649-conjugated anti-GPIb-beta antibody. The femurs were rendered transparent by the CUBIC method as previously described (Cell 159, 911-24 (2014)) and examined using confocal microscopy; and found that platelets/MKs co-localized within MM.1S GFP+-infiltrated BM niches. Further confirmation of the co-localization of MM cells and MKs was performed using immunohistochemistry (CD138+ and GPIb-alpha+). We next investigated the effect of platelets on MM cell proliferation: MM cells, where co-cultured with platelets and found that platelets enhanced the proliferation rate of MM cells in a platelet number-dependent manner, as shown by using BrdU (p<0.001). The observed platelet-dependent induction of MM cells proliferation was also demonstrated by using platelet aggregation releasate. We next performed RNA sequencing studies using MM cells and platelet-interacting MM cells, and demonstrated that platelet-interacting MM cells presented with enrichment for signaling pathways such as TGF-beta as compared to MM cell control. We performed cytokine array analysis and confirmed that several cytokines, including TGF-beta, ENA-78, SDF-1, and TARC, were released from platelets activated by co-culture with MM cells. We next investigated the effect of platelets on MM tumor growth in vivo, by using bioluminescence imaging (BLI). MM cells were pre-cultured with platelets for 2 days, washed and then intravenously injected into SCID/Beige mice (n=6). We found a significantly higher MM tumor burden in mice injected with MM cell pre-cultured with platelets, as compared to control mice where buffer treated MM cells were used (p<0.01), together with reduced survival (p=0.0011). These findings indicate the ability of platelets to enhance MM cell growth in vivo. To further confirm the role of platelets in mediating MM tumor growth, we performed platelet depletion by treating mice with an anti-platelet antibody (R300, 4 ug/g IP injection), and subsequently injected MM cells intravenously. We found that platelet-depleted mice presented with decreased MM tumor growth (p<0.05) and improved survival rate compared to control mice treated with IgG isotype control (p=0.0044). These findings indicate that MM cells induce platelet aggregation and interact with platelets/MKs within the BM. Importantly, MM cell-platelet interaction is responsible for the activation of pro-survival signaling pathways in MM cells at transcriptome level, leading to enhanced MM cell proliferation, as shown both in vitro and in vivo. Disclosures No relevant conflicts of interest to declare.

scholarly journals Circ-DONSON Knockdown Inhibits Cell Proliferation and Radioresistance of Breast Cancer Cells via Regulating SOX4

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xiufang Zhu ◽  
Lei Li
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cell Survival ◽  
Cell Lines ◽  
Caspase 3 ◽  
Biological Role ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay

Background. Circular RNAs have been validated as critical regulators in the development of breast cancer (BC). Circ-DONSON is involved in the progression of glioma and gastric cancer. However, the biological role of circ-DONSON in BC remains unclear, and the aim of this study was to explore the biological role of circ-DONSON in BC. Methods. Human tissue samples and BC cell lines were collected in this study. siRNAs against circ-DONSON were transfected into BC cell lines for silencing of circ-DONSON. Quantitative real-time PCR was used to test the circ-DONSON expression. Cell counting kit-8 (CCK-8), 5-bromo-2′ deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA), colony formation, and caspase-3 activity assays were used to assess cell proliferation, cell survival, and cell viability. Western blotting analysis was used to detect the protein expression levels. Results. Our findings showed that circ-DONSON showed high expression in BC tissues and cell lines. CCK-8 and BrdU-ELISA assays showed that circ-DONSON knockdown inhibited BC cell proliferation. Moreover, cell survival, cell viability, and caspase-3 activity assays showed that circ-DONSON knockdown reduced the radioresistance of BC cells. Mechanistically, circ-DONSON regulated BC cell proliferation and radioresistance via SRY-box transcription factor 4 (SOX4). SOX4 overexpression significantly rescued the effect of circ-DONSON knockdown on BC cell proliferation and radioresistance. Moreover, circ-DONSON activated the Wnt/β-catenin pathway in BC cells via SOX4. Conclusion. Our study concluded that circ-DONSON knockdown hindered cell proliferation and radioresistance through the SOX4/Wnt/β-catenin pathway in BC.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

2021 ◽  
Vol 22 (8) ◽  
pp. 3804
Author(s):  
Luisa Siculella ◽  
Laura Giannotti ◽  
Benedetta Di Chiara Stanca ◽  
Matteo Calcagnile ◽  
Alessio Rochira ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Negative Correlation ◽  
Cancer Biology ◽  
Human Tumor ◽  
In Silico Analysis ◽  
Proliferation Rate ◽  
Reactive Intermediate ◽  
Cell Proliferation Rate

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.

scholarly journals Kras-driven intratumoral heterogeneity triggers infiltration of M2 polarized macrophages via the circHIPK3/PTK2 immunosuppressive circuit

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Theodora Katopodi ◽  
Savvas Petanidis ◽  
Kalliopi Domvri ◽  
Paul Zarogoulidis ◽  
Doxakis Anestakis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Lung Tumor ◽  
Quantitative Polymerase Chain Reaction ◽  
Macrophage Polarization ◽  
Metastatic Potential ◽  
Intratumoral Heterogeneity ◽  
M2 Macrophage

AbstractIntratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.

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 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.

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