CircEXOC6B Suppresses the Proliferation and Motility and Sensitizes Ovarian Cancer Cells to Paclitaxel Through miR-376c-3p/FOXO3 Axis.

Cancer biotherapy & radiopharmaceuticals Pub Date : 2022-11-01 Epub Date: 2020-10-02 DOI:10.1089/cbr.2020.3739
Yingchun Zheng, Zhen Li, Shiying Yang, Yue Wang, Zhaohui Luan
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引用次数: 21

Abstract

Background: Circular RNAs (circRNAs) are regarded as important regulators in the tumorigenesis of multiple cancers. However, the characterization of circRNA exocyst complex component 6B (circEXOC6B) in ovarian cancer is barely known. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the enrichment of circEXOC6B, microRNA-376c-3p (miR-376c-3p), and forkhead box O3 (FOXO3). Cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay and colony formation assay. Cell metastasis was measured by transwell assays. Western blot assay was conducted to examine the expression of proliferation and metastasis-related proteins and FOXO3. The chemoresistance of ovarian cancer cells was analyzed by CCK8 assay. Flow cytometry was used to detect cell apoptosis. The activities of caspase3 and caspase9 were analyzed through using colorimetric assay kits. The direct interaction between miR-376c-3p and circEXOC6B or FOXO3 was predicted by StarBase software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft assay was conducted to verify the role of circEXOC6B on the paclitaxel (PTX) resistance of ovarian cancer cells in vivo. Results: The level of circEXOC6B was notably decreased in ovarian cancer tissues. Low level of circEXOC6B was associated with malignant pathological characteristics in ovarian cancer patients. CircEXOC6B suppressed the proliferation and motility and decreased the chemoresistance of ovarian cancer cells to PTX. CircEXOC6B functioned through directly targeting and downregulating miR-376c-3p. FOXO3 was a direct target of miR-376c-3p, and the abundance of FOXO3 was regulated by circEXOC6B/miR-376c-3p axis. CircEXOC6B accelerated the PTX sensitivity of ovarian cancer cells through acting as a decoy of miR-376c-3p to upregulate FOXO3 in vivo. Conclusion: CircEXOC6B suppressed the progression and PTX resistance of ovarian cancer cells through sequestering miR-376c-3p, thus enhancing FOXO3 level.

CircEXOC6B通过miR-376c-3p/FOXO3轴抑制卵巢癌细胞对紫杉醇的增殖和运动敏化。
背景:环状rna (circRNAs)被认为是多种癌症发生过程中的重要调控因子。然而,circRNA外囊复合物组分6B (circEXOC6B)在卵巢癌中的特性却鲜为人知。材料与方法:采用实时荧光定量聚合酶链反应(qRT-PCR)检测circEXOC6B、microRNA-376c-3p (miR-376c-3p)和叉头盒O3 (FOXO3)的富集程度。细胞计数试剂盒-8 (CCK8)法和集落形成法检测细胞增殖。用transwell法测定细胞转移。Western blot检测细胞增殖转移相关蛋白及FOXO3的表达。采用CCK8法分析卵巢癌细胞的化疗耐药情况。流式细胞术检测细胞凋亡。采用比色法检测caspase3和caspase9活性。通过StarBase软件预测miR-376c-3p与circEXOC6B或FOXO3之间的直接相互作用,并通过双荧光素酶报告基因实验和RNA免疫沉淀(RIP)实验证实。通过小鼠异种移植实验验证了circEXOC6B在体内对卵巢癌细胞紫杉醇(PTX)耐药的作用。结果:circEXOC6B在卵巢癌组织中表达水平明显降低。低水平的circEXOC6B与卵巢癌患者的恶性病理特征相关。CircEXOC6B抑制卵巢癌细胞对PTX的增殖和运动,降低化疗耐药。CircEXOC6B通过直接靶向和下调miR-376c-3p发挥作用。FOXO3是miR-376c-3p的直接靶点,FOXO3的丰度受circEXOC6B/miR-376c-3p轴调控。CircEXOC6B通过作为miR-376c-3p在体内上调FOXO3的诱饵,加速了卵巢癌细胞对PTX的敏感性。结论:CircEXOC6B通过分离miR-376c-3p抑制卵巢癌细胞的进展和PTX耐药,从而提高FOXO3水平。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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