miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer

Abstract Background Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. Methods MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. Results miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. Conclusion miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.

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MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8

Frontiers in Oncology ◽

10.3389/fonc.2021.581932 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lili Zhang ◽

Huixiao Chen ◽

Fengxi He ◽

Shiqian Zhang ◽

Aihua Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cell Lines ◽

Cancer Progression ◽

Target Gene ◽

Migration And Invasion ◽

Cancer Cell Proliferation

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

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Hypermethylation of mismatch repair gene hMSH2 associates with platinum-resistant disease in epithelial ovarian cancer

Clinical Epigenetics ◽

10.1186/s13148-019-0748-4 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Hua Tian ◽

Li Yan ◽

Li Xiao-fei ◽

Sun Hai-yan ◽

Chen Juan ◽

...

Keyword(s):

Mass Spectrometry ◽

Ovarian Cancer ◽

Dna Methylation ◽

Epithelial Ovarian Cancer ◽

Upstream Region ◽

Platinum Resistance ◽

Maldi Tof Mass Spectrometry ◽

Platinum Resistant ◽

Aberrant Dna Methylation ◽

Low Expression

Abstract Purpose One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance. Methods By initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of the hMSH2 gene was discovered hypermethylated in the platinum-resistant group. The effect of hMSH2 methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels of hMSH2 upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect the hMSH2 mRNA and protein expression in extended 150 patients. Results RRBS assay discovered an upstream region from − 1193 to − 1125 of hMSH2 was significant hypermethylated in resistant EOC patients (P = 1.06 × 10−14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. Knockdown hMSH2 reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation of hMSH2 upstream region with platinum resistance. Spearman’s correlation analysis revealed a significantly negative connection between methylation level of hMSH2 upstream region and its expression. The Kaplan-Meier analyses showed the high methylation of hMSH2 promoter region, and its low expressions are associated with worse survival. In multivariable models, hMSH2 low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85–2.31). Conclusion The hypermethylation of hMSH2 upstream region is associated with platinum resistant in EOC, and low expression of hMSH2 may be an index for the poor prognosis.

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Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000484458 ◽

2017 ◽

Vol 43 (6) ◽

pp. 2489-2504 ◽

Cited By ~ 16

Author(s):

Le Chen ◽

Ying Yao ◽

Lijuan Sun ◽

Jiajia Zhou ◽

Minmin Miao ◽

...

Keyword(s):

Ovarian Cancer ◽

Alternative Splicing ◽

Epithelial Ovarian Cancer ◽

Epithelial Mesenchymal Transition ◽

Regulatory Protein ◽

Cell Counting ◽

Migration And Invasion ◽

Mesenchymal Transition

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

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The Inhibitory Effect of KIAA1456 on the Proliferation and Metastasis of Epithelial Ovarian Cancer Through SSX1 and AKT Signaling Pathway

10.21203/rs.3.rs-950951/v1 ◽

2021 ◽

Author(s):

Yingfeng Zhang ◽

Yanhong Gao ◽

Congcong Sun ◽

Yanhua Mao ◽

Benyuan Wu ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Tumour Growth ◽

Molecular Mechanisms ◽

Signalling Pathway ◽

Migration And Invasion ◽

Ovarian Tumours ◽

Proliferation And Metastasis ◽

Epithelial Ovarian Tumours

Abstract Background: KIAA1456 is effective in the inhibition of tumorigenesis. We previously confirmed that KIAA1456 inhibits cell proliferation and metastasis in epithelial ovarian tumours. In the current study, the specific molecular mechanisms and clinical significance of KIAA1456 underlying the repression of epithelial ovarian cancer were investigated.Methods: Immunohistochemistry was used to evaluate the protein expression of KIAA1456 and SSX1 in epithelial ovarian tumours and normal ovarian tissues. The relationship of KIAA1456 and SSX1 with overall survival of patients with epithelial ovarian cancer was analysed with Kaplan–Meier survival curve and log-rank tests. KIAA1456 was overexpressed and silenced in HO8910PM cells with a lentivirus. The anticancer activity of KIAA1456 was tested by CCK8, plate clone formation assay, flow cytometry, wound healing assay and Transwell invasion assay. Xenograft tumour models were used to investigate the effects of KIAA1456 on tumour growth in vivo. Bioinformatics analyses of microarray profiling indicated that SSX1 and the PI3K/AKT signalling pathway were differentially expressed in KIAA1456-overexpressing and control cells. Therefore, the biological function of HO8910PM cotransfected with KIAA1456- and SSX1-overexpressing cells was detected to validate the rescue effect of SSX1. The downstream factors of PI3K/AKT that are related to cell growth and apoptosis, including p-AKT, PCNA, MMP9, CyclinD1 and Bcl-2, were detected by Western blot analysis.Results: KIAA1456 expression was lower in epithelial ovarian tumours than in normal ovarian tissues. Its expression level negatively correlated with pathological grade. Pearson’s correlation analysis showed that KIAA1456 negatively correlated with SSX1 expression. The overexpression of KIAA1456 in HO8910PM cells inhibited proliferation, migration and invasion and promoted apoptosis. By contrast, the silencing of KIAA1456 resulted in the opposite behaviour. A xenograft tumour experiment showed that KIAA1456 overexpression inhibited tumour growth in vivo. Mechanistically, the overexpression of KIAA1456 inhibited SSX1 expression and AKT phosphorylation in HO8910PM cells, causing the inactivation of the AKT signalling pathway and eventually reducing the expression of PCNA, CyclinD1, MMP9 and Bcl2. Similarly, the silencing of KIAA1456 resulted in the opposite behaviour. Finally, SSX1 overexpression could partially reverse the KIAA1456-induced biological effect.Conclusion: KIAA1456 may serve as a tumour suppressor via the inactivation of SSX1 and the AKT pathway, providing a promising therapeutic target for epithelial ovarian cancers.

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

10.21203/rs.3.rs-51729/v3 ◽

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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LY2157299 Monohydrate, a TGF-βR1 Inhibitor, Suppresses Tumor Growth and Ascites Development in Ovarian Cancer

Cancers ◽

10.3390/cancers10080260 ◽

2018 ◽

Vol 10 (8) ◽

pp. 260 ◽

Cited By ~ 9

Author(s):

Qing Zhang ◽

Xiaonan Hou ◽

Bradley Evans ◽

Jamison VanBlaricom ◽

Saravut Weroha ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Cell Lines ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Migration And Invasion ◽

Ascites Formation ◽

Tgf Β1

Transforming growth factor beta (TGF-β) signaling has pleiotropic functions regulating cancer initiation, development, and metastasis, and also plays important roles in the interaction between stromal and cancer cells, making the pathway a potential therapeutic target. LY2157299 monohydrate (LY), an inhibitor of TGF-β receptor I (TGFBRI), was examined for its ability to inhibit ovarian cancer (OC) growth both in high-grade serous ovarian cancer (HGSOC) cell lines and xenograft models. Immunohistochemistry, qRT-PCR, and Western blot were performed to study the effect of LY treatment on expression of cancer- and fibroblast-derived genes. Results showed that exposure to TGF-β1 induced phosphorylation of SMAD2 and SMAD3 in all tested OC cell lines, but this induction was suppressed by pretreatment with LY. LY alone inhibited the proliferation, migration, and invasion of HGSOC cells in vitro. TGF-β1-induced fibroblast activation was blocked by LY. LY also delayed tumor growth and suppressed ascites formation in vivo. In addition, independent of tumor inhibition, LY reduces ascites formation in vivo. Using OVCAR8 xenograft specimens we confirmed the inhibitory effect of LY on TGF-β signaling and tumor stromal expression of collagen type XI chain 1 (COL11A1) and versican (VCAN). These observations suggest a role for anti-TGF-β signaling-directed therapy in ovarian cancer.

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Chemokine CXCL-2 Regulates Resistance to Platinum in Epithelial Ovarian Cancer by Mediating ATR/CHK1 Signaling Pathway

10.21203/rs.3.rs-90867/v1 ◽

2020 ◽

Author(s):

Sipei Nie ◽

Yicong Wan ◽

Hui Wang ◽

Jinhui Liu ◽

Jing Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Signaling Pathway ◽

Cancer Cell ◽

Treatment Strategies ◽

Cell Cycle Checkpoint ◽

Platinum Resistance ◽

Platinum Resistant ◽

Cell Assays

Abstract Backgrounds：Platinum-resistance remains a challenge to recurrence and metastasis of epithelial ovarian cancer (EOC) and the mechanisms are unidentified. Tumor microenvironment (TME) and chemokine might play a key role in tumor chemoresistance. This study is designed to reveal the important role of CXCL-2 in causing EOC platinum-resistance. Materials and Methods: Differently expressed chemokines were selected based on the GSE114206 dataset of GEO database. Chemokines levels of platinum-sensitive and platinum-resistant EOC. Cell assays were performed and the cell stem characteristics were investigated for exploring the roles of CXCL-2 in EOC chemoresistance. We further explored the downstream signaling pathway regulated by CXCL-2 by detecting the expression of related molecules and rescue assay with the signaling inhibitor.Results: CXCL-2, CXCL-11 and CXCL-13 were found up-regulated in platinum-resistant EOC based on GSE114206 databases, and CXCL-2 was identified as key chemokine by validation. The cell assays showed overexpressing CXCL-2 and co-culturing with recombinant human CXCL-2 promoted cancer cell chemoresistance. Conversely, knocking down CXCL-2 and co-culturing with neutralizing antibody to CXCL-2 reduced cisplatin-resistance in cisplatin-resistant EOC cells. CXCL-2 levels regulated the stemness of cancer cells and activated ataxia telangiectasia and Rad3-related (ATR)/cell cycle checkpoint kinase1 (CHK1) signaling pathway. The cancer cell chemoresistance can be saved by CXCL-2 receptor inhibitor (SB225002) and CHK1 inhibitor (SAR-020106) in vitro. Conclusion: These results identified a CXCL-2 mediated platinum-resistance mechanism in EOC, and provided a novel target for chemoresistance prevention and treatment strategies.

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

Frontiers in Oncology ◽

10.3389/fonc.2021.751567 ◽

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.

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LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00889-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qi Yang ◽

Yu-Jie Dong

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Noncoding Rna ◽

Tumor Xenograft ◽

Migration And Invasion ◽

Epithelial Cell Line ◽

Invasion And Migration ◽

And Migration

Abstract Background Ovarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo. Results Significant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified. Conclusion SNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.

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

10.21203/rs.3.rs-51729/v1 ◽

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.

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