OncoTargets and Therapy (Oct 2020)
AZIN1-AS1, A Novel Oncogenic LncRNA, Promotes the Progression of Non-Small Cell Lung Cancer by Regulating MiR-513b-5p and DUSP11
Abstract
Yong Cai,1,* Qiongya Wu,1,* Yu Liu,1,* Jiying Wang2 1Department of Radiotherapy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China; 2Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiying WangDepartment of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, People’s Republic of ChinaEmail [email protected]: 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.Methods: 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.Results: 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.Conclusion: AZIN1-AS1 acts as a tumor promoter in NSCLC, which is ascribed to the regulation of miR-513b-5p and DUSP11.Keywords: non-small cell lung cancer, AZIN1-AS1, miR-513b-5p, DUSP11
