<p>AZIN1-AS1, A Novel Oncogenic LncRNA, Promotes the Progression of Non-Small Cell Lung Cancer by Regulating MiR-513b-5p and DUSP11</p>

Abstract

Background: Emerging researches have demonstrated that aberrantly expressed long noncoding 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.

DUSP11 and triphosphate RNA balance during virus infection

“…Recently, it was reported that DUSP11 acts on the TGF-β activated kinase 1 (TAK1) protein preventing a lethal inflammatory response of mice that are exposed to the bacterial PAMP lipopolysaccharide (LPS) [ 28 ]. Further, Cai and colleagues show that DUSP11 can promote proliferation in cellular transformation assays, which they speculate could be due to protein substrates of DUSP11 [ 29 ]. However, given that the DUSP11 catalytic site structure is typical of RNA phosphatases, and that DUSP11 shows preferentially enhanced activity on RNA over peptide substrates [ 19 – 21 ], it is unclear how large a role peptide substrates will play in the biology associated with DUSP11.…”

Dual-Specificity Phosphatases and Kidney Diseases

“…Unlike miRNAs, lncRNAs can function indirectly, either via binding with miRNAs or recruiting other proteins. Recently, lncRNA AZIN1 was found to downregulate miR-513b-5p via sponging it, which in turn targeted DUSP11 in tumor tissues [26]. More interestingly, another study shows that lncRNA CASC9 could recruit histone methyltransferase EZH2 to be epigenetic regulate DUSP1/MKP1 expression in non-small cell lung cancer [27].…”

miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1

“…Previous studies have shown that miR-513b-5p can play a unique role in different types of solid tumors. For example, the expression of miR-513b-5p is significantly downregulated in non-small cell lung cancer (NSCLC) [ 8 , 9 ] and gastric cancer [ 10 ]. Its exogenous overexpression can significantly inhibit the proliferation, invasion, migration, and promote apoptosis of NSCLC [ 8 , 9 ] and gastric cancer cells [ 10 ].…”

“…For example, the expression of miR-513b-5p is significantly downregulated in non-small cell lung cancer (NSCLC) [ 8 , 9 ] and gastric cancer [ 10 ]. Its exogenous overexpression can significantly inhibit the proliferation, invasion, migration, and promote apoptosis of NSCLC [ 8 , 9 ] and gastric cancer cells [ 10 ]. However, some studies have also reported that miR-513b-5p plays an oncogene in cervical cancer [ 11 ] and ovarian cancer [ 12 ].…”