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环状 RNA circSLC8A1 通过靶向 miR-106b-5p/FOXJ3 轴抑制非小细胞肺癌细胞的增殖和侵袭。

Circular RNA circSLC8A1 inhibits the proliferation and invasion of non-small cell lung cancer cells through targeting the miR-106b-5p /FOXJ3 axis.

机构信息

Department of Respiratory and Critical Care Medicine, HanZhong Central Hospital, Hanzhong, China.

出版信息

Cell Cycle. 2021 Dec;20(24):2597-2606. doi: 10.1080/15384101.2021.1995968. Epub 2021 Nov 1.

Abstract

Circular RNA derived from the gene (circSLC8A1) has been implicated in the pathogenesis of several types of cancers. However, the role of circSLC8A1 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, the expression levels of circSLC8A1 in NSCLC tissues and cell lines were determined by qRT-PCR analysis. Function-gain-assays were then carried out to further validate the role of circSLC8A1 in NSCLC . Online prediction software and the subsequent luciferase reporter assay were used to identify the target genes of circSLC8A1 and microRNA (miR)-106b-5p. CircSLC8A1 was found to be downregulated in NSCLC tissues and cell lines. Overexpression of circSLC8A1 significantly inhibited the proliferation and invasion of NSCLC cells. Further investigations shown that circSLC8A1 was able to bind to miR-106b-5p as well as inhibit the expression of miR-106b-5p in NSCLC cells. MiR-106b-5p mimics reversed the inhibitory effects of circSLC8A1 overexpression on cell proliferation and invasion. Furthermore, we found that forkhead box J3 (FOXJ3) to be a target gene of miR-106b-5p in NSCLC cells. Knockdown of FOXJ3 reversed the inhibitory effects of miR-106b-5p inhibitor on cell proliferation and invasion. Collectively, these findings indicate that circSLC8A1 exhibits anti-tumor activity in NSCLC, which might be mediated by the miR-106b-5p/FOXJ3 axis. The circSLC8A1/miR-106b-5p/FOXJ3 axis may thus represent a promising therapeutic target for the management of NSCLC.

摘要

环状 RNA 来源于基因 (circSLC8A1),与多种类型癌症的发病机制有关。然而,circSLC8A1 在非小细胞肺癌 (NSCLC) 中的作用尚不清楚。在本研究中,通过 qRT-PCR 分析测定了 NSCLC 组织和细胞系中 circSLC8A1 的表达水平。然后进行功能获得性测定,以进一步验证 circSLC8A1 在 NSCLC 中的作用。在线预测软件和随后的荧光素酶报告基因测定用于鉴定 circSLC8A1 和 microRNA (miR)-106b-5p 的靶基因。发现 circSLC8A1 在 NSCLC 组织和细胞系中下调。circSLC8A1 的过表达显著抑制 NSCLC 细胞的增殖和侵袭。进一步研究表明,circSLC8A1 能够与 miR-106b-5p 结合,并抑制 NSCLC 细胞中 miR-106b-5p 的表达。miR-106b-5p 模拟物逆转了 circSLC8A1 过表达对细胞增殖和侵袭的抑制作用。此外,我们发现 FOXJ3 是 NSCLC 细胞中 miR-106b-5p 的靶基因。FOXJ3 的敲低逆转了 miR-106b-5p 抑制剂对细胞增殖和侵袭的抑制作用。总之,这些发现表明 circSLC8A1 在 NSCLC 中具有抗肿瘤活性,可能是通过 miR-106b-5p/FOXJ3 轴介导的。因此,circSLC8A1/miR-106b-5p/FOXJ3 轴可能成为 NSCLC 治疗的有前途的治疗靶点。

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