Hsa_circ_0063804 enhances ovarian cancer cells proliferation and resistance to cisplatin by targeting miR-1276/CLU axis

Jun You, Yuwen Han, Hai-feng Qiao, Yun Han, Xiaona Lu, Yiling Lu, XiaoYun Wang, Haili Kai, Yan-Li Zheng
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引用次数: 4

Abstract

Purpose: This article researched circ_0063804 effects on ovarian cancer (OC) development and resistance to cisplatin, aiming to provide a new target for OC therapy. Methods: A total of 108 OC patients participated in this study. The circle structure of circ_0063804 was investigated using RNase R. Circ_0063804 expression in OC cells were up-regulated or down-regulated by transfection. Cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Flow cytometry was used to detect apoptosis. OC cells resistance to cisplatin was explored through MTT assay. Luciferase reporter assay was performed. qRT-PCR and Western blot was applied to research genes expression. Xenograft tumor experiment was conducted using nude mice. Ki67 expression in xenograft tumor was detected by immunohistochemistry. Results: Circ_0063804 expression was up-regulated in OC patients and indicated poor prognosis (P < 0.05). Circ_0063804 had a stable circle structure. Circ_0063804 enhanced proliferation, resistance to cisplatin and reduced apoptosis of OC cells (P < 0.01). miR-1276 was down-regulated in OC patients and sponged by circ_0063804. CLU was directly inhibited by miR-1276 and up-regulated in OC patients. Circ_0063804 exacerbated malignant phenotype and resistance to cisplatin of OC cells in vitro by enhancing CLU expression via sponging miR-1276 (P < 0.01). Circ_0063804 silencing inhibited OC cells growth, resistance to cisplatin and Ki67 expression in vivo (P < 0.01). Conclusion: Circ_0063804 promoted OC cells proliferation and resistance to cisplatin by enhancing CLU expression via sponging miR-1276.
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Hsa_circ_0063804通过靶向miR-1276/CLU轴增强卵巢癌细胞增殖和顺铂耐药
目的:研究circ_0063804对卵巢癌(OC)发展及顺铂耐药的影响,为卵巢癌治疗提供新的靶点。方法:共108例OC患者参与本研究。利用RNase r对circ_0063804的环状结构进行了研究,circ_0063804在OC细胞中的表达上调或下调。采用细胞计数试剂盒-8法和菌落形成法检测细胞增殖情况。流式细胞术检测细胞凋亡。MTT法观察卵巢癌细胞对顺铂的耐药性。荧光素酶报告试验。应用qRT-PCR和Western blot技术研究基因表达。采用裸鼠进行异种移植瘤实验。免疫组化法检测Ki67在异种移植瘤中的表达。结果:Circ_0063804在OC患者中表达上调,预后较差(P < 0.05)。Circ_0063804具有稳定的圆结构。Circ_0063804增强OC细胞增殖、顺铂耐药、减少凋亡(P < 0.01)。miR-1276在OC患者中下调,并被circ_0063804擦拭。CLU被miR-1276直接抑制,在OC患者中上调。Circ_0063804通过海绵miR-1276增强CLU的表达,加重了体外OC细胞的恶性表型和对顺铂的耐药性(P < 0.01)。Circ_0063804沉默抑制OC细胞生长、顺铂耐药及体内Ki67表达(P < 0.01)。结论:Circ_0063804通过海绵化miR-1276增强CLU表达,促进OC细胞增殖和顺铂耐药。
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