Department of Breast and Thyroid, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
Editorial Department of Chinese Journal of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Pathol Int. 2020 Dec;70(12):953-964. doi: 10.1111/pin.13011. Epub 2020 Sep 1.
Accumulating studies authenticate that circular RNAs (circRNAs) are involved in the progression of cancers. However, their role in breast cancer (BC) remains largely unknown. In this study, real-time polymerase chain reaction was employed to detect the circ_0000291 and miR-326 expressions in BC tissues and cells. The correlation between the expression level of circ_0000291 and clinicopathological parameters of BC patients was analyzed. Western blot was used to detect the expression of E26 transformation-specific sequence-1 (ETS1), E-cadherin, N-cadherin and Vimentin in BC cells. Cell proliferation was measured using the cell counting kit-8 assay and the bromodeoxyuridine assay. Cell migration and invasion were detected by Transwell assay. The interactions between circ_0000291 and miR-326, miR-326 and ETS1 were verified using bioinformatics prediction, the dual-luciferase reporter gene assay or/and RNA binding protein immunoprecipitation assay. We demonstrated that circ_0000291 was significantly upregulated in BC, and its high expression was positively correlated with T stage and local lymph node metastasis. Functional assays validated that circ_0000291 promoted BC cell proliferation, migration and invasion. The mechanism studies indicated that circ_0000291 could decoy miR-326 and in turn upregulate the expression of ETS1. In conclusion, circ_0000291 is the novel oncogenic circRNA and promotes BC progression via modulating the miR-326/ETS1 axis.
越来越多的研究证实,环状 RNA(circRNAs)参与了癌症的进展。然而,它们在乳腺癌(BC)中的作用在很大程度上仍然未知。在本研究中,采用实时聚合酶链反应检测 BC 组织和细胞中 circ_0000291 和 miR-326 的表达。分析 circ_0000291 的表达水平与 BC 患者临床病理参数之间的相关性。Western blot 用于检测 BC 细胞中 E26 转化特异性序列-1(ETS1)、E-钙黏蛋白、N-钙黏蛋白和波形蛋白的表达。使用细胞计数试剂盒-8 测定法和溴脱氧尿苷测定法测量细胞增殖。通过 Transwell 测定法检测细胞迁移和侵袭。使用生物信息学预测、双荧光素酶报告基因测定或/和 RNA 结合蛋白免疫沉淀测定法验证 circ_0000291 与 miR-326、miR-326 与 ETS1 之间的相互作用。我们证明 circ_0000291 在 BC 中显著上调,其高表达与 T 分期和局部淋巴结转移呈正相关。功能测定验证了 circ_0000291 促进了 BC 细胞的增殖、迁移和侵袭。机制研究表明,circ_0000291 可以诱捕 miR-326,并反过来上调 ETS1 的表达。总之,circ_0000291 是一种新型致癌环状 RNA,通过调节 miR-326/ETS1 轴促进 BC 进展。