Hedgehog−Gli2 Signaling Promotes Chemoresistance in Ovarian Cancer Cells by Regulating MDR1

BackgroundCisplatin (DDP) resistance remains a key challenge in improving the clinical outcome of patients with ovarian cancer (OC). Gli2 overexpression can lead to DDP resistance in OC cells, but the specific underlying regulatory mechanism remains unclear. The membrane transporter encoding gene MDR1 positively regulates chemotherapy resistance in various cancer types. We evaluated MDR1 as a potential Gli2 downstream target and the contribution of the Gli2/MDR1 axis in promoting DDP resistance in OC cells.MethodsTo generate drug-resistant SKOV3/DDP cells, SKOV3 cells were grown for six months under continuous induction wherein the DDP concentration was steadily increased. Gli2 expression in OC cells with varying DDP sensitivities was detected using western blot. Cell counting kit-8 assays were used to assess the DDP sensitivity of SKOV3, SKOV3/DDP, A2780, and A2780/DDP cells and reversal of DDP resistance in SKOV3/DDP and A2780/DDP cells. Cell proliferation was analyzed using 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The transcriptional regulation of MDR1 by Gli2 was determined using luciferase reporter assays. Finally, xenograft OC tumors were generated in nude mice, which were then treated with intraperitoneal DDP or phosphate-buffered saline (PBS) injections to investigate if Gli2 affected DDP resistance in OC in vivo.ResultsDDP-resistant SKOV3/DDP and A2780/DDP cells showed higher expression of Gli2 and MDR1 as compared with that in DDP-sensitive OC cells. Gli2 knockdown in SKOV3/DDP cells significantly reduced MDR1 expression, whereas it increased DNA damage, thereby sensitizing OC cells to DDP. Similar results were obtained after targeting Gli2 expression with the Gli-antagonist 61 inhibitor (GANT61) in SKOV3/DDP and A2780/DDP cells. In cells stably overexpressing Gli2, treatment with gradient concentrations of verapamil, an MDR1 inhibitor, significantly inhibited MDR1 expression. Our findings indicate that downregulation of MDR1 expression may reverse OC cell resistance to DDP. Moreover, dual-luciferase reporter gene assays confirmed that MDR1 is a direct downstream target of Gli2, with Gli2 positively regulating MDR1 expression. Finally, subcutaneous xenotransplantation in nude mice demonstrated that Gli2 plays a key role in regulating OC drug resistance.ConclusionsWe identified a mechanism by which Hedgehog-Gli signaling regulates OC chemoresistance by modulating MDR1 expression. Hence, Gli2 and MDR1 are potential biomarkers and therapeutic targets in patients with chemoresistant OC.

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Circ-VPS13C enhances cisplatin resistance in ovarian cancer via modulating miR-106b-5p/YWHAZ axis

Archives of Medical Science ◽

10.5114/aoms/133038 ◽

2021 ◽

Author(s):

Hairong Yao ◽

Dantong Liu ◽

Fangyuan Gao ◽

Qian Li ◽

Shikai Liu

Keyword(s):

Ovarian Cancer ◽

Western Blot ◽

Chemotherapy Resistance ◽

Cell Counting ◽

Luciferase Reporter ◽

Circular Rnas ◽

Western Blot Assay ◽

Inhibition Concentration ◽

And Migration

IntroductionOvarian cancer (OC) is the malignant tumor with the highest mortality among gynecological cancers. Chemotherapy resistance is a major obstacle to OC therapy. Circular RNAs (circRNAs) play crucial roles in cancer development and chemoresistance. However, the role and potential mechanism of has-circ-001567 (circ-VPS13C) in chemoresistance of OC remain unknown.Material and methodsThe levels of circ-VPS13C, miR-106b-5p and 14-3-3 zeta (YWHAZ) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit-8 (CCK-8) assay was used to assess cell viability and calculate the half inhibition concentration (IC50) of cisplatin (DDP). The levels of autophagy-related markers were measured by western blot assay. Cell apoptosis and migration were evaluated by flow cytometry and transwell assay, respectively. The binding relationship between miR-106b-5p and circ-VPS13C or YWHAZ was confirmed by dual-luciferase reporter assay. Xenograft assay was performed to explore the role of circ-VPS13C in vivo.ResultsCirc-VPS13C and YWHAZ were up-regulated, while miR-106b-5p was down-regulated in DDP-resistant OC tissues and cells. Knockdown of circ-VPS13C enhanced DDP sensitivity by repressing autophagy in DDP-resistant cells. Circ-VPS13C increased DDP resistance via sponging miR-106b-5p. Moreover, miR-106b-5p directly targeted YWHAZ. Up-regulation of YWHAZ alleviated the decrease in DDP resistance caused by circ-VPS13C depletion. In addition, circ-VPS13C silencing decreased DDP resistance in vivo.ConclusionsCirc-VPS13C knockdown enhanced DDP sensitivity of OC through modulation of autophagy via the miR-106b-5p/YWHAZ axis, providing a new biomarker for improving the efficacy of OC chemotherapy.

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Circular RNA Hsa_Circ_0007444 Inhibits Tumor Progression Through MiR-23a-3p/DICER1 in Ovarian Cancer

10.21203/rs.3.rs-955306/v1 ◽

2021 ◽

Author(s):

Min Zhang ◽

Yu Sun ◽

Hanzi Xu ◽

Yaqian Shi ◽

Rong Shen ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Cell Lines ◽

Xenograft Model ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Mouse Xenograft Model

Abstract Background: Circular RNAs are a class of non-coding regulatory RNAs reported to be involved in cancer development and progression. Previous studies, including our own, have indicated that hsa_circ_0007444 was downregulated in ovarian cancer (OC) tissues. Herein, we demonstrated another mechanism of hsa_circ_0007444 in ovarian cancer.Methods: The expression of hsa_circ_0007444, miR-23a-3p, and DICER1 were determined by quantitative real-time PCR. Cell proliferation, invasion, migration, and apoptosis were examined by cell counting kit 8, transwell, and flow cytometry assays. The roles of hsa_circ_0007444 in tumor growth and metastasis were assessed in vivo using a nude mouse xenograft model. The bioinformatics tools were employed to predict the binding sites, which were then verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. DICER1 protein level was measured by western blot. Results: Hsa_circ_0007444 was downregulated in ovarian cancer cell lines compared with normal ovarian epithelial cell lines. Also, gain- and loss-of-function results indicated that hsa_circ_0007444 inhibited cell proliferation, invasion, migration, increased cell apoptosis of ovarian cancer cells in vitro, and impaired tumor growth and lung metastasis in vivo. Additionally, the results of the bioinformatics analysis, RIP, dual-luciferase reporter, and rescue assays confirmed that hsa_circ_0007444 could interact with AGO2 and sponge miR-23a-3p, thereby upregulating DICER1 expression, which was an important tumor suppressor in ovarian cancer.Conclusion: We found that overexpressed hsa_circ_0007444 could inhibit ovarian cancer progression through the hsa_circ_0007444/miR-23a-3p/DICER1 axis.

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DDP-resistant ovarian cancer cells-derived exosomal microRNA-30a-5p reduces the resistance of ovarian cancer cells to DDP

Open Biology ◽

10.1098/rsob.190173 ◽

2020 ◽

Vol 10 (4) ◽

pp. 190173 ◽

Cited By ~ 1

Author(s):

Ronghua Liu ◽

Yucan Zhang ◽

Peiwen Sun ◽

Changxiu Wang

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Quantitative Polymerase Chain Reaction ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Important Conclusion ◽

Skov3 Cells ◽

Potential Strategy

Exosomes carrying microRNAs (miRNAs) have been demonstrated to play critical roles in the regulation of development, growth and metastasis of cancer. Bioinformatic predictions identified differentially expressed SRY-box 9 (SOX9) in OC, and the regulatory miRNA miR-139-5p. Here, we aim to evaluate the function of exosomal miR-139-5p in the sensitivity of ovarian cancer (OC) cells to cis-diamminedichloroplatinum(II) (DDP). Expression pattern of miR-139-5p and SOX9 in ovarian cancer cells (SKOV3) and DDP-resistant cells (SKOV3/DDP) was identified using reverse transcription quantitative polymerase chain reaction and western blot analysis. The relationship between miR-139-5p and SOX9 was validated using a dual-luciferase reporter assay. SKOV3/DDP cell line was developed and introduced with miR-30a-5p mimic to analyse the effects of miR-30a-5p on resistance to DDP. The in vitro and in vivo effects of exosomal miR-30a-5p on resistance of SKOV3 cells to DDP were assessed in a co-culture system of exosomes and OC cells as well as in tumour-bearing nude mice. High expression of SOX9 and low expression of miR-30-5p were witnessed in OC. Furthermore, miR-30-5p, a downregulated miRNA in SKOV3/DDP cells, increased the rate of cell apoptosis and enhanced the sensitivity of SKOV3/DDP cells to DDP by targeting SOX9. Moreover, exosomes carrying miR-30a-5p were identified to sensitize SKOV3/DDP cells to DDP both in vitro and in vivo . These data together supported an important conclusion that DDP-resistant OC cell-derived exosomal miR-30a-5p enhanced cellular sensitivity to DDP, highlighting a potential strategy to overcome drug resistance.

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MicroRNA-200c suppresses epithelial-mesenchymal transition of ovarian cancer by targeting cofilin-2

10.1101/449587 ◽

2018 ◽

Author(s):

Xuechen Yu ◽

Yuanzhen Zhang ◽

Wei Zhang ◽

Huijun Chen

Keyword(s):

Ovarian Cancer ◽

Epithelial Mesenchymal Transition ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Skov3 Cells ◽

And Migration

AbstractThis study investigated the effects of microRNA-200c (miR-200c) and cofilin-2 (CFL2) in regulating epithelial-mesenchymal transition (EMT) in ovarian cancer. The level of miR-200c was lower in invasive SKOV3 cells than that in non-invasive OVCAR3 cells, whereas CFL2 showed the opposite trend. Bioinformatics analysis and dual-luciferase reporter gene assays indicated that CFL2 was a direct target of miR-200c. Furthermore, SKOV3 and OVCAR3 cells were transfected with miR-200c mimic or inhibitor, pCDH-CFL2 (CFL2 overexpression), or CFL2 shRNA (CFL2 silencing). MiR-200c inhibition and CFL2 overexpression resulted in elevated levels of both CFL2 and vimentin while reducing E-cadherin expression. They also increased ovarian cancer cell invasion and migrationin vitroandin vivoand increased the tumor volumes. Conversely, miR-200c mimic and CFL2 shRNA exerted the opposite effects as those aforementioned. In addition, the effects of pCDH-CFL2 and CFL2 shRNA were reversed by the miR-200c mimic and inhibitor, respectively. This finding suggested that miR-200c could be a potential tumor suppressor by targeting CFL2 in the EMT process.

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TRIAP1 Inhibition Activates the Cytochrome c/Apaf-1/Caspase-9 Signaling Pathway to Enhance Human Ovarian Cancer Sensitivity to Cisplatin

Chemotherapy ◽

10.1159/000501633 ◽

2019 ◽

Vol 64 (3) ◽

pp. 119-128 ◽

Cited By ~ 1

Author(s):

Tian-Mei Zhang

Keyword(s):

Ovarian Cancer ◽

Nude Mice ◽

Cell Apoptosis ◽

Caspase 9 ◽

Ovarian Carcinoma Cell Line ◽

Skov3 Cells ◽

Cyt C ◽

Sirna Group

Objective: To investigate whether TRIAP1inhibition affects the ovarian cancer cell resistance to cisplatin (DDP) via the Cyt c/Apaf-1/caspase-9 pathway by in vitro and in vivo experiments. Methods: CCK8 assay was performed to find out how treatment with both TRIAP1 siRNA and DDP affects the cell viability of SKOV3 cells and DDP-resistant human ovarian carcinoma cell line SKOV3/DDP. SKOV3/DDP cells were transfected with control siRNA or TRIAP1 siRNA before 24 h of treatment with DDP (5 μg/mL). Flow cytometry was employed to detect cell apoptosis and Western blot to examine the expressions of Cyt c/Apaf-1/caspase-9 pathway-related proteins. SKOV3/DDP cells transfected with control siRNA or TRIAP1 siRNA were subcutaneously injected into BALB/c-nu/nu nude mice followed by the intraperitoneal injection of DDP (4 mg/kg). Cyt c/Apaf-1/caspase-9 pathway in transplanted tumors was detected by immunohistochemistry. Results: TRIAP1 expression declined in SKOV3 cells when compared with SKOV3/DDP cells. The proliferation rate was lower in SKOV3/DDP cells transfected with TRIAP1 siRNA combined with treatment of DDP (1, 2, 4, 6, 8, 16, 32 μg/mL) than in those transfected with control siRNA. Moreover, the TRIAP1 siRNA group had an increased SKOV3/DDP cell apoptosis rate with the activation of the Cyt c/Apaf-1/caspase-9 pathway. During DDP treatment, nude mice in TRIAP1 siRNA group had slower growth and smaller size of transplanted tumor than those in control siRNA group, with increased expression of Cyt c, Apaf-1, and caspase-9. Conclusion: TRIAP1 inhibition may enhance the sensitivity of SKOV3/DDP cells to cisplatin via activation of the Cyt c/Apaf-1/caspase-9 pathway.

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Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway

Cancer Cell International ◽

10.1186/s12935-020-01666-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Zhenhua Du ◽

Lei Wang ◽

Yu Xia

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Western Blot ◽

Gynecologic Cancer ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Western Blot Assay

Abstract Background Ovarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism. Methods The levels of circ_0015756, microRNA-942-5p (miR-942-5p) and Cullin 4B (CUL4B) were determined by quantitative real-time PCR (qRT-PCR) or Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and transwell assay. The levels of proliferation-related and metastasis-related proteins were measured by Western blot assay. The relationship between miR-942-5p and circ_0015756 or CUL4B was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft assay was used to analyze tumor growth in vivo. Results Circ_0015756 and CUL4B levels were increased, while miR-942-5p level was decreased in OC tissues and cells. Depletion of circ_0015756 suppressed proliferation, migration and invasion and promoted apoptosis in OC cells. Down-regulation of circ_0015756 hindered OC cell progression via modulating miR-942-5p. Also, up-regulation of miR-942-5p impeded OC cell development by targeting CUL4B. Mechanistically, circ_0015756 up-regulated CUL4B via sponging miR-942-5p. Moreover, circ_0015756 silencing inhibited tumor growth in vivo. Conclusion Knockdown of circ_0015756 suppressed OC progression via regulating miR-942-5p/CUL4B axis, suggesting that circ_0015756 might be a potential therapeutic target for ovarian cancer.

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MicroRNA-137-mediated inhibition of lysine-specific demethylase-1 prevents against rheumatoid arthritis in an association with the REST/mTOR axis

Molecular Pain ◽

10.1177/17448069211041847 ◽

2021 ◽

Vol 17 ◽

pp. 174480692110418

Author(s):

Wei Sun ◽

Yijun Zhang ◽

Guanghui Wang

Keyword(s):

Rheumatoid Arthritis ◽

Mtor Pathway ◽

Cell Counting ◽

Inflammatory Factors ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Luciferase Reporter Gene ◽

Lysine Specific Demethylase ◽

Gene Assay

Background It has been increasingly reported that microRNAs (miRNAs) are related to rheumatoid arthritis (RA) pathogenesis. This present research was conducted to analyze the functions of miR-137 and the underlying molecular mechanism in RA progression. Methods Differentially expressed miRNAs in RA patients were analyzed using microarray-based analyses. Next, experiments involving miR-137 overexpression were performed to analyze the role of miR-137 in human fibroblast-like synoviocytes-RA (HFLS-RA) using cell counting kit-8 (CCK-8) assay, EdU staining, Transwell assay and flow cytometry, respectively. The function of miR-137 in inflammation was determined using ELISA. The binding relationship between miR-137 and LSD1 was confirmed by dual-luciferase reporter gene assay and ChIP test. Besides, a rat model with RA was established for in vivo experiments. Results miR-137 was downregulated in RA tissues and cells, which was negatively correlated with inflammatory factors. Upregulated miR-137 suppressed growth, migration and invasion of HFLS-RA, but promoted apoptosis. Lysine-specific demethylase-1 (LSD1) was a target of miR-137 and could be negatively regulated by miR-137. Moreover, LSD1 could activate REST through demethylation, while the REST/mTOR pathway induced levels of pro-inflammatory factors in RA. We observed the similar results in our in vivo study. Conclusion This study suggested that miR-137 reduced LSD1 expression to inhibit the activation of REST/mTOR pathway, thus preventing against inflammation and ameliorating RA development. Our research may offer new insights into treatment of RA.

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Long Non-coding RNA CCAT1 Sponges miR-454 to Promote Chemoresistance of Ovarian Cancer Cells to Cisplatin by Regulation of Surviving

Cancer Research and Treatment ◽

10.4143/crt.2019.498 ◽

2020 ◽

Vol 52 (3) ◽

pp. 798-814 ◽

Cited By ~ 3

Author(s):

De-Ying Wang ◽

Na Li ◽

Yu-Lan Cui

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cell Line ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Qrt Pcr ◽

Non Coding Rna ◽

Induced Apoptosis ◽

Long Non Coding Rna

PurposeColon cancer-associated transcript 1 (CCAT1) was identified as an oncogenic long non-coding RNA (lncRNA) in a variety of cancers. However, there was a lack of understanding of the mechanism by which CCAT1 conferred cisplatin (also known as DDP) resistance in ovarian cancer cells.Materials and MethodsCell viability of A2780, SKOV3, A2780/DDP, and SKOV3/DDP cells upon cisplatin treatment was monitored by MTT assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression levels of CCAT1 and miR-454. The effect of sh-CCAT1 on cisplatin response was investigated in xenografts study. Bioinformatic analysis, luciferase reporter assay and qRT-PCR were conducted to validate the direct interaction among CCAT1, miR-454, and survivin. Apoptosis was determined by flow cytometry after dual staining of Annexin-V-FITC/propidium iodide, and the expression of apoptosis-related proteins Bcl-2, Bax and survivin were detected by qRT-PCR and Western blotting. Xenograft study was conducted to monitor in vivo tumor formation.ResultsCCAT1 was highly expressed in cisplatin-resistant ovarian cancer cell line A2780/DDP and SKOV3/DDP. Knockdown of CCAT1 restored sensitivity to cisplatin in vitro and in vivo. Our data revealed that silencing of CCAT1 promoted cisplatin-induced apoptosis via modulating the expression of pro- or anti-apoptotic proteins Bax, Bcl-2, and survivin. CCAT1 directly interacted with miR-454, and miR-454 overexpression potentiated cisplatin-induced apoptosis. Survivin was identified as a functional target of miR-454, restoration of survivin attenuated the effect of miR-454 on cisplatin response. In addition, miR-454 inhibitor or overexpression of survivin was found to abolish sh-CCAT1–induced apoptosis upon cisplatin treatment.ConclusionCCAT1/miR-454/survivin axis conferred cisplatin resistance in ovarian cancer cells.

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PRPF6 Induces the Alternative Splicing of lncRNA SNHG16 To Promote Progression and Paclitaxel Resistance of Ovarian Cancer via Regulating GATA3 Transcription

10.21203/rs.3.rs-1045802/v1 ◽

2021 ◽

Author(s):

Han Wang ◽

Yingying Zhou ◽

Siyang Zhang ◽

Ya Qi ◽

Min Wang

Keyword(s):

Ovarian Cancer ◽

Alternative Splicing ◽

Epithelial To Mesenchymal Transition ◽

Binding Protein ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Mesenchymal Transition ◽

Gene Assay

Abstract Background Small nucleolar RNA host gene 16 (SNHG16) and pre-mRNA processing factor 6(PRPF6) play vital roles in regulatory mechanisms of multiple cancers, but the mechanisms in ovarian cancer (OC) remains poorly understood. Methods The expression of SNHG16 transcripts-SNHG16-L/S in OC tissues were analyzed by real-time PCR (RT-PCR). The expression of PRPF6 in OC tissues were detected by Immunohistochemistry (IHC). Tumorigenesis, epithelial-to-mesenchymal transition (EMT) and PTX-resistance were detected by western blot, transwell, CCK-8 assays, colony formation assays and flow cytometry analyses. Molecular interactions were examined by dual-luciferase reporter gene assay, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP). Results The results indicated the expression of SNHG16-L/S was opposite in chemo-resistance and chemo-sensitivity tissues of OC. And SNHG16-L/S had different effects on the progression and PTX-resistance of OC cells. SNHG16-L inhibited GATA binding protein 3 (GATA3) transcription through CCAAT/enhancer-binding protein b (CEBPB) to further promote tumorigenesis, EMT and PTX-resistance of OC. Moreover, PRPF6 was upregulated in chemo-resistance tissues of OC. PRPF6 promoted tumorigenesis and PTX-resistance in vitro and in vivo. Mechanistically, PRPF6 induced the alternative splicing of SNHG16 to downregulate SNHG16-L, which further mediated progression and PTX-resistance through upregulating GATA3 in OC. Conclusions Totally, the results demonstrated that PRPF6 promoted progression and PTX-resistance in OC through SNHG16-L/CEBPB/GATA3 axis. Thus, PRPF6 may become a valuable target for OC therapy.

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NEAT1 Overexpression Indicates a Poor Prognosis and Induces Chemotherapy Resistance via the miR-491-5p/SOX3 Signaling Pathway in Ovarian Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.616220 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xinzhuan Jia ◽

Lan Wei ◽

Zhengmao Zhang

Keyword(s):

Ovarian Cancer ◽

Cell Lines ◽

Cell Apoptosis ◽

Expression Patterns ◽

Chemotherapy Resistance ◽

Direct Interaction ◽

Luciferase Reporter ◽

Tissue Samples ◽

Qrt Pcr

BackgroundAccumulated studies have reported that dysregulated long non-coding RNAs (lncRNAs) are crucial in ovarian cancer (OC) initiation and development. However, detailed biological functions of lncRNA NEAT1 during the progression of OC remains to be uncovered.PurposeOur aim was to identify the role of NEAT1 in cisplatin resistance of ovarian cancer and the underlying mechanisms.MethodsThe expression patterns of NEAT1 in OC cell lines and tissue samples were identified by qRT-PCR. The cisplatin (DDP) sensitivity of OC cells was detected by MTT and CCK8 assay, while OC cell apoptosis and cell cycle were detected using flow cytometer assays. In addition, effects of NEAT1 on tumor growth were determined by xenograft tumor model. Luciferase reporter assay was conducted to prove the regulatory relation of miR-491-5p, NEAT1, and SOX3. Importantly, the expression of NEAT1 in exosomes from cisplatin-resistant patients was also determined by using qRT-PCR.ResultsIn this study, upregulated NEAT1 was detected in OC cell lines and tissues. Meanwhile, NEAT1 was also increased in cisplatin-resistant OC cell lines and tissues. Upregulation of NEAT1 inhibited cisplatin-induced OC cell apoptosis and promoted cell proliferation, while knockdown of NEAT1 played the opposite role. These effects were also observed in vivo. Furthermore, direct interaction was observed between NEAT1 and miR-491-5p. NEAT1 led to the upregulation of miR-491-5p-targeted SOX3 mRNA. Importantly, this study also showed upregulated NEAT1 expression in serum exosomes derived from cisplatin-resistant patients.ConclusionNEAT1 is vital in the chemoresistance of ovarian cancer through regulating miR-491-5p/SOX3 pathway, showing that NEAT1 might be a potential target for OC resistance treatment.

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