Circ_0070203 Promotes Epithelial-mesenchymal Transition in Ovarian Serous Cystadenocarcinoma through miR-370-3p/TGFβR2 Axis

IF 2.5 4区 医学 Q3 ONCOLOGY
Qiong Tang, Huiting Wen, Haoyue Hu, Xiaoli Chen, Shuxiu Xu, Li Fan, Longyang Liu, Jing Li
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Abstract

Introduction: Circular RNAs (circRNAs) are important biological molecules associated with the pathogenesis of multiple cancers. Objective: This work aimed to investigate the function and molecular mechanism of circ_0070203 in high-grade serous ovarian cystadenocarcinoma (HGSOC). Methods: circRNA microarray was conducted to detect the circ_0070203 expression in HGSOC tissues. Bioinformatics analysis was used to find the binding sites between circ_0070203, miR- 370-3p and TGFβR2. Real-time quantitative reverse transcription PCR (RT-qPCR) was executed to detect the expressions of circ_0070203, miR-370-3p and TGFβR2 in HGSOC tissues and SKOV3 cells. Dual-luciferase reporter gene assay was used to validate the relationships between miR-370-3p and circ_0070203 or TGFβR2. Besides, transwell assays were conducted to assess the migrative, invasive abilities of ovarian cancer (OC) cells. Western blotting was adopted to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. The related patents were also studied during the research. Results: Circ_0070203 and TGFβR2 were upregulated, while miR-370-3p was downregulated in FIGO stage Ⅲ-Ⅳ HGSOC tissues and SKOV-3 cell lines. circ_0070203 overexpression changed the expression of other EMT-related proteins and enhanced the migrative, invasive abilities of OC cells, while silencing circ_0070203 worked oppositely. Mechanistically, circ_0070203 could upregulate TGFβR2 expression in OC cells via sponging miR-370-3p. Conclusion: Circ_0070203 could promote the epithelial-mesenchymal transition, invasion, and metastasis of HGSOC via regulating the miR-370-3p/TGFβR2 axis. Our findings provided a potential biomarker for HGSOC therapy.
Circ_0070203通过miR-370-3p/ tgf - β r2轴促进卵巢浆液性囊腺癌上皮-间质转化
环状rna (circRNAs)是与多种癌症发病机制相关的重要生物分子。目的:探讨circ_0070203在高级别浆液性卵巢囊腺癌(HGSOC)中的作用及分子机制。方法:采用circRNA芯片检测circ_0070203在HGSOC组织中的表达。利用生物信息学分析找到circ_0070203、miR- 370-3p和tgf - β r2之间的结合位点。采用实时定量反转录PCR (RT-qPCR)检测circ_0070203、miR-370-3p和tgf - β r2在HGSOC组织和SKOV3细胞中的表达。采用双荧光素酶报告基因检测验证miR-370-3p与circ_0070203或tgf - β r2之间的关系。此外,还进行了transwell试验来评估卵巢癌(OC)细胞的迁移和侵袭能力。采用Western blotting检测上皮-间质转化(epithelial-mesenchymal transition, EMT)相关蛋白的表达。研究过程中还对相关专利进行了研究。结果:Circ_0070203和TGFβR2在FIGO期Ⅲ-ⅣHGSOC组织和SKOV-3细胞系中表达上调,miR-370-3p表达下调。过表达circ_0070203改变了其他emt相关蛋白的表达,增强了OC细胞的迁移和侵袭能力,而沉默circ_0070203则相反。机制上,circ_0070203可通过海绵miR-370-3p上调OC细胞中tgf - β r2的表达。结论:Circ_0070203可通过调节miR-370-3p/ tgf - β r2轴促进HGSOC的上皮-间质转化、侵袭转移。我们的发现为HGSOC治疗提供了一个潜在的生物标志物。
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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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