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Hsa_circ_0063804 通过靶向 miR-1276/CLU 轴促进卵巢癌细胞增殖和对顺铂的耐药性。

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

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.

出版信息

Aging (Albany NY). 2022 Jun 10;14(11):4699-4713. doi: 10.18632/aging.203474.

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 ( < 0.05). Circ_0063804 had a stable circle structure. Circ_0063804 enhanced proliferation, resistance to cisplatin and reduced apoptosis of OC cells ( < 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 by enhancing CLU expression via sponging miR-1276 ( < 0.01). Circ_0063804 silencing inhibited OC cells growth, resistance to cisplatin and Ki67 expression ( < 0.01).

CONCLUSION

Circ_0063804 promoted OC cells proliferation and resistance to cisplatin by enhancing CLU expression via sponging miR-1276.

摘要

目的

本研究旨在探讨 circ_0063804 对卵巢癌(OC)发展和顺铂耐药性的影响,为 OC 治疗提供新靶点。

方法

本研究纳入了 108 名 OC 患者。通过 RNase R 检测 circ_0063804 的环状结构。通过转染上调或下调 OC 细胞中的 circ_0063804 表达。用细胞计数试剂盒-8 法和集落形成实验评估细胞增殖。用流式细胞术检测细胞凋亡。通过 MTT 实验探讨 OC 细胞对顺铂的耐药性。通过荧光素酶报告实验进行研究。用 qRT-PCR 和 Western blot 检测基因表达。利用裸鼠进行异种移植肿瘤实验。通过免疫组化检测异种移植肿瘤中 Ki67 的表达。

结果

OC 患者中 circ_0063804 表达上调,且预示着不良预后(<0.05)。circ_0063804 具有稳定的环状结构。circ_0063804 增强了 OC 细胞的增殖、顺铂耐药性并降低了细胞凋亡(<0.01)。OC 患者中 miR-1276 表达下调,并与 circ_0063804 结合。CLU 直接受到 miR-1276 的抑制,且在 OC 患者中上调。circ_0063804 通过海绵吸附 miR-1276 增强 CLU 表达,从而加剧 OC 细胞的恶性表型和对顺铂的耐药性(<0.01)。沉默 circ_0063804 抑制 OC 细胞生长、顺铂耐药性和 Ki67 表达(<0.01)。

结论

circ_0063804 通过海绵吸附 miR-1276 增强 CLU 表达,促进 OC 细胞增殖和对顺铂的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d37/9217714/829d02f973f7/aging-14-203474-g001.jpg

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