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Hsa_circ_0102171 通过靶向 miR-4465/CREBRF 轴促进宫颈癌的进展。

Hsa_circ_0102171 aggravates the progression of cervical cancer through targeting miR-4465/CREBRF axis.

机构信息

The 5th Ward of Radiotherapy Department of Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.

出版信息

J Cell Physiol. 2021 Jul;236(7):4973-4984. doi: 10.1002/jcp.30210. Epub 2020 Dec 7.

Abstract

Cervical cancer (CC) has caused numerous cancer-related deaths in women. Recent years, circular RNAs have been reported as vital factors in CC tumorigenesis. Our current study focused on the role of hsa_circ_0102171 (called circ_0102171 subsequently) in CC. At first, we applied reverse transcription polymerase chain reaction to detect the expression of circ_0102171 in CC tissues and cells. Subsequently, we silenced circ_0102171 to conduct loss-of-function assays, including cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, Transwell assay, and flow cytometry analysis. Interestingly, we discovered that circ_0102171 expressed at a high level in CC tissues and cells. Functionally, silencing circ_0102171 prohibited cell proliferation, migration and invasion, and strengthened cell apoptosis in CC in vitro. Mechanistic investigations revealed that circ_0102171 could act as a sponge for miR-4465. Gain-of-function assays demonstrated that miR-4465 hindered the growth and migration of CC cells. Moreover, circ_0102171 enhanced the level of CREB3 regulatory factor (CREBRF) which was the downstream target of miR-4465. Rescue assays suggested that CREBRF and miR-4465 could involve in circ_0102171-mediated CC progression. Finally, in vivo data supported that silencing circ_0102171 hindered CC cell growth. In conclusion, circ_0102171 aggravates CC progression via targeting miR-4465/CREBRF axis.

摘要

宫颈癌(CC)导致了许多与癌症相关的女性死亡。近年来,环状 RNA 被报道为 CC 肿瘤发生的重要因素。我们目前的研究集中在 hsa_circ_0102171(称为 circ_0102171 随后)在 CC 中的作用。首先,我们应用逆转录聚合酶链反应检测 CC 组织和细胞中 circ_0102171 的表达。随后,我们沉默 circ_0102171 进行功能丧失测定,包括细胞计数试剂盒-8 测定、5-乙炔基-2'-脱氧尿苷染色、Transwell 测定和流式细胞术分析。有趣的是,我们发现 circ_0102171 在 CC 组织和细胞中表达水平较高。功能上,沉默 circ_0102171 可抑制 CC 细胞在体外的增殖、迁移和侵袭,并增强细胞凋亡。机制研究表明,circ_0102171 可以作为 miR-4465 的海绵。功能获得实验表明,miR-4465 抑制 CC 细胞的生长和迁移。此外,circ_0102171 增强了 miR-4465 的下游靶标 CREB3 调节因子(CREBRF)的水平。挽救实验表明,CREBRF 和 miR-4465 可能参与 circ_0102171 介导的 CC 进展。最后,体内数据支持沉默 circ_0102171 可抑制 CC 细胞生长。总之,circ_0102171 通过靶向 miR-4465/CREBRF 轴加重 CC 进展。

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