Abstract
Long non-coding RNAs (lncRNAs), as competitive endogenous RNAs (ceRNAs), play a critical role in biological processes of cancer. However, the roles of specific lncRNAs in ceRNA network of lung adenocarcinoma (LUAD) remains largely unclear. Herein, we identified the roles of lncRNA ADAMTS9-AS1/AS2 (ADAMTS-AS1/AS2) in lung adenocarcinoma by bioinformatics analyses and functional verification. First, differentially expressed genes ADAMTS9-AS1, ADAMTS9-AS2 and ADAMTS9 were screened out from GSE130779. Then the expression correlation of these three genes was analyzed. The results showed that ADAMTS9-AS1, ADAMTS9-AS2 and ADAMTS9 were down-regulated in LUAD, and were positively correlated with each other. After that, miRcode was used to find miR-150 which binds to ADAMTS9-AS1/ADAMTS9-AS2/ADAMTS9. Next, co-expression analysis and functional enrichment analyses were performed to further analyze differentially expressed genes. The results showed that the differentially expressed genes were mainly enriched in Beta3 integrin cell surface interactions and epithelial-to-mesenchymal transition. Finally, the cell functions of ADAMTS9-AS1 and ADAMTS9-AS2 in A549 and NCI-H1299 cell lines were verified. In vitro cell studies confirmed that ADAMTS9-AS1 and ADAMTS9-AS2 play an inhibitory role in LUAD cells.
Highlights
Lung cancer is the leading cause of cancer-related death [1]
Through a series of bioinformatics analyses, we found ADAMTS9-AS1/ADAMTS9-AS1 could competitively bind miR-150 to rescue the inhibition of ADAMTS9 by miR-150, and regulate the migration and invasion of lung adenocarcinoma (LUAD) cells by influencing on Beta3 integrin cell surface interactions or epithelial-to-mesenchymal transition signaling pathway
The five Long non-coding RNAs (lncRNAs) (FENDRR, LINC00472, FGF14-IT1, ADAMTS9-AS1, and LINC00641) with the significant downregulation were selected for expression verification in LUAD cell lines and human normal lung epithelial cells
Summary
Lung cancer is the leading cause of cancer-related death [1]. There are 1.8 million people diagnosed with lung disease, and 1.6 million people die from it [2]. Lung adenocaricinoma (LUAD), known as pulmonary adenocarcinoma, is a type of non-small-cell lung carcinoma (NSCLC) and accounts for approximately 40% of all lung cancers [3, 4]. Despite great improvements in LUAD research and treatment, the prognosis for LUAD patients remains poor and the mortality rates have not been improved significantly [5]. In order to improve the prognosis of patients with LUAD, it is urgent to identify the molecular mechanism, which is of great significance to find effective biomarkers for the early diagnosis. Long non-coding RNAs (lncRNAs), as a novel
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