AZIN1-AS1, A Novel Oncogenic LncRNA, Promotes the Progression of Non-Small Cell Lung Cancer by Regulating MiR-513b-5p and DUSP11.
AZIN1-AS1, A Novel Oncogenic LncRNA, Promotes the Progression of Non-Small Cell Lung Cancer by Regulating MiR-513b-5p and DUSP11.
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DOI：
10.2147/ott.s261497
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发表时间：
2020
影响因子：
4
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Cai Y;Wu Q;Liu Y;Wang J
近年来的研究表明，异常表达的长链非编码RNA（lncRNA）在非小细胞肺癌（NSCLC）的发生、发展过程中具有重要意义。本研究旨在探讨lncRNA AZIN 1反义RNA 1（AZIN 1-AS 1）在NSCLC中的作用及其机制。采用qRT-PCR方法检测AZIN 1-AS 1和miR-513 b-5 p在NSCLC组织中的表达。在体外测定中使用NSCLC细胞系（H1299和HCC 827）。采用CCK-8法、EdU法、创伤愈合实验和Transwell法检测AZIN 1-AS 1对NSCLC细胞的生物学效应。建立小鼠皮下移植瘤模型和小鼠尾静脉注射模型，检测AZIN 1-AS 1在体内的作用。通过生物信息学分析、qRT-PCR、Western印迹和荧光素酶报告基因测定来确定AZIN 1-AS 1与miR-513 b-5 p、miR-513 b-5 p和双特异性磷酸酶11（DUSP 11）之间的相互作用。AZIN 1-AS 1在NSCLC细胞和组织中表达上调，而miR-513 b-5 p表达下调。沉默AZIN 1-AS 1或过表达miR-513 b-5 p可明显抑制非小细胞肺癌细胞的增殖、迁移和侵袭，而过表达AZIN 1-AS 1或抑制miR-513 b-5 p则作用相反。重要的是，AZIN 1-AS 1介导的促进NSCLC细胞恶性化的作用被miR-513 b-5 p模拟物逆转。AZIN 1-AS 1可通过海绵状作用下调miR-513 b-5 p的表达，且AZIN 1-AS 1表达与miR-513 b-5 p表达呈负相关。AZIN 1-AS 1也能促进DUSP 11的表达，证明DUSP 11是miR-513 b-5 p的靶基因。进一步的体内实验表明，沉默AZIN 1-AS 1可降低肿瘤的生长和转移，并伴随着肿瘤组织中miR-513 b-5 p的过表达和DUSP 11的抑制。AZIN 1-AS 1在NSCLC中作为肿瘤促进剂发挥作用，这归因于miR-513 b-5 p和DUSP 11的调节。
Emerging researches have demonstrated that aberrantly expressed long non-coding RNAs (lncRNAs) have great significance in non-small cell lung cancer (NSCLC) progression. The aim of this study was to explore the role of lncRNA AZIN1 antisense RNA 1 (AZIN1-AS1) in NSCLC and the related mechanism. Expressions of AZIN1-AS1 and miR-513b-5p in NSCLC samples were detected by qRT-PCR. NSCLC cell lines (H1299 and HCC827) were used in vitro assays. CCK-8 assay, EdU assay, wound healing test and Transwell assay were carried out to test the biological influence of AZIN1-AS1 on NSCLC cells. Subcutaneous xenotransplanted tumor model and tail vein injection model were established to test the role of AZIN1-AS1 in vivo. Interactions between AZIN1-AS1 and miR-513b-5p, miR-513b-5p and dual-specificity phosphatase 11 (DUSP11) were determined by bioinformatic analysis, qRT-PCR, Western blot, and luciferase reporter assay. AZIN1-AS1 was up-regulated in NSCLC cells and tissues, while miR-513b-5p was significantly down-regulated. Silencing of AZIN1-AS1 or overexpression of miR-513b-5p markedly inhibited proliferation, migration and invasion of NSCLC cells, while overexpression of AZIN1-AS1 or inhibition of miR-513b-5p functioned oppositely. Importantly, AZIN1-AS1 mediated the promotion of malignancy of NSCLC cells was reversed by miR-513b-5p mimics. What’s more, AZIN1-AS1 could down-regulate miR-513b-5p via sponging it, and there existed a negative correlation between AZIN1-AS1 expression and miR-513b-5p expression in NSCLC samples. AZIN1-AS1 also enhanced the expression levels of DUSP11, which was proved as a target gene of miR-513b-5p. Further in vivo experiments showed that silencing of AZIN1-AS1 decreased tumor growth and metastasis, which was accompanied by overexpression of miR-513b-5p and inhibition of DUSP11 in tumor tissues. AZIN1-AS1 acts as a tumor promoter in NSCLC, which is ascribed to the regulation of miR-513b-5p and DUSP11.