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长链非编码 RNA DLX6-AS1 通过靶向 miR-424-5p 增加 WEE1 的表达促进肝癌。

Long noncoding RNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p.

机构信息

Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

Department of Otolaryngology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

出版信息

J Cell Biochem. 2019 Aug;120(8):12290-12299. doi: 10.1002/jcb.28493. Epub 2019 Feb 25.

Abstract

Long noncoding RNAs (lncRNAs) played an important role in tumorigenesis and development of hepatocellular carcinoma (HCC). In this study, we first demonstrated that lncRNA DLX6 antisense RNA 1 (DLX6-AS1) was upregulated in cancer tissues and cells lines compared with normal adjacent and cell line. Knock-down DLX6-AS1 by transfection with small interfering RNA (siRNA) suppressed cell proliferation, migration, and invasion of HCC cells. Cell cycle analysis showed that cells transfected with siRNA were arrested in G0/G1 phase. Then, we performed dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay to show that DLX6-AS1 could bind with miR-424-5p. And cotransfection inhibitor of miR-424-5p with siRNA of DLX6-AS1 could abolish the inhibitory effect of siRNA of DLX6-AS1 on cell proliferation, migration, and invasion. Moreover, we further demonstrated that the oncogene WEE1 G2 checkpoint kinase (WEE1) was the target of miR-424-5p and expression levels of WEE1 were positive correlation with that of DLX6-AS1. Taken together, these results suggested that upregulated DLX6-AS1 promoted cell proliferation, migration, and invasion of HCC through increasing expression of WEE1 via targeting miR-424-5p.

摘要

长链非编码 RNA(lncRNA)在肝癌(HCC)的发生和发展中起着重要作用。在本研究中,我们首先证明与正常相邻组织和细胞系相比,lncRNA DLX6 反义 RNA 1(DLX6-AS1)在肿瘤组织和细胞系中上调。用小干扰 RNA(siRNA)转染敲低 DLX6-AS1 抑制 HCC 细胞的增殖、迁移和侵袭。细胞周期分析表明,转染 siRNA 的细胞停滞在 G0/G1 期。然后,我们进行了双荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)实验,表明 DLX6-AS1 可以与 miR-424-5p 结合。并且共转染 miR-424-5p 抑制剂和 siRNA 的 DLX6-AS1 可以消除 siRNA 的 DLX6-AS1 对细胞增殖、迁移和侵袭的抑制作用。此外,我们进一步证明癌基因 WEE1 G2 检查点激酶(WEE1)是 miR-424-5p 的靶基因,并且 WEE1 的表达水平与 DLX6-AS1 的表达水平呈正相关。总之,这些结果表明上调的 DLX6-AS1 通过靶向 miR-424-5p 增加 WEE1 的表达促进 HCC 细胞的增殖、迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e6a/6712946/4fd1a71d84cf/JCB-120-12290-g001.jpg

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