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环状 RNA 0000514 通过调控 miR-296-5p/CXCL10 轴促进乳腺癌进展。

Circ_0000514 promotes breast cancer progression by regulating the miR-296-5p/CXCL10 axis.

出版信息

J Biochem. 2022 Jan 7;170(6):753-761. doi: 10.1093/jb/mvab097.

Abstract

The biological function of circular RNA 0000514 (circ_0000514) in breast cancer (bc) is still unknown. In this study, we downloaded the microarray dataset GSE101123 from Gene Expression Omnibus database and then analysed the differentially expressed circular RNAs in bc tissues compared with adjacent tissues, and we demonstrated that circ_0000514 was up-regulated in bc tissues. Circ_0000514, miR-296-5p and CXC chemokine ligand10 (CXCL10) expressions in bc tissues and cell lines were probed by quantitativereal-time polymerase chain reaction and Western blot. Cell counting kit-8, 5-bromo-2'-deoxyuridine and transwell assays were adopted to determine the cell viability, proliferation, migration and invasion. The targeting relationship between miR-296-5p and circ_0000514 or CXCL10 3'-UTR was predicted by bioinformatics and validated by dual-luciferase reporter assay. We demonstrated that circ_0000514 and CXCL10 expressions were raised in bc tissues and cell lines while miR-296-5p expression was declined. Circ_0000514 knockdown could inhibit the proliferation, migration and invasion of bc cells and miR-296-5p overexpression also suppressed the malignant phenotypes of bc cells. Mechanistically, miR-296-5p was identified as the downstream target of circ_0000514 and could be inhibited by circ_0000514. Moreover, CXCL10 was the target of miR-296-5p, whose expression could be indirectly and positively regulated by circ_0000514. In conclusion, circ_0000514 is involved in bc progression via regulating miR-296-5p/CXCL10 axis. Graphical Abstract.

摘要

环状 RNA 0000514(circ_0000514)在乳腺癌(bc)中的生物学功能尚不清楚。在本研究中,我们从基因表达综合数据库中下载了微阵列数据集 GSE101123,并分析了 bc 组织与相邻组织中差异表达的环状 RNA,结果表明 circ_0000514 在 bc 组织中上调。通过定量实时聚合酶链反应和 Western blot 检测 bc 组织和细胞系中 circ_0000514、miR-296-5p 和 CXC 趋化因子配体 10(CXCL10)的表达。采用细胞计数试剂盒-8、5-溴-2'-脱氧尿苷和 Transwell 测定法来确定细胞活力、增殖、迁移和侵袭。通过生物信息学预测 miR-296-5p 与 circ_0000514 或 CXCL10 3'-UTR 的靶向关系,并通过双荧光素酶报告基因实验验证。结果表明,circ_0000514 和 CXCL10 在 bc 组织和细胞系中表达上调,而 miR-296-5p 表达下调。circ_0000514 敲低可抑制 bc 细胞的增殖、迁移和侵袭,而过表达 miR-296-5p 也可抑制 bc 细胞的恶性表型。机制上,miR-296-5p 被鉴定为 circ_0000514 的下游靶标,并可被 circ_0000514 抑制。此外,CXCL10 是 miR-296-5p 的靶标,其表达可间接和正被 circ_0000514 调节。总之,circ_0000514 通过调节 miR-296-5p/CXCL10 轴参与 bc 的进展。

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