Long noncoding RNA LINC00968 inhibits proliferation, migration and invasion of lung adenocarcinoma through  targeting  miR-22-5p / CDC14A  axis

Abstract

Background Lung adenocarcinoma (LUAD) is a high aggressive human cancer which usually diagnosed at advanced stages. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) are crucial participants in LUAD progression. Methods The mRNA levels of LINC00968, miR-22-5p and cell division cycle 14A (CDC14A) were measured using quantitative real-time PCR. Cell proliferation was evaluated using cell counting kit-8 and flow cytometry. Cell migration and cell invasion were assessed by wound healing and transwell assay, respectively. The interactions between LINC00968 and miR-22-5p were validated by RNA immunoprecipitation, RNA pull down and luciferase reporter assay. Results We found that lncRNA LINC00968 was significantly down-regulated in LUAD tissues and cell lines. LINC00968 level was positively correlated to survival rate, and negatively correlated to tumor node metastasis stage, tumor size and lymph node metastasis of LUAD patients. LINC00968 over-expression in LUAD cells inhibited cell proliferation and induced cell cycle arrest at G1 phase. LINC00968 over-expression also suppressed migration, invasion and epithelial mesenchymal transition (EMT) as evidenced by elevated E-cadherin, decreased N-cadherin, TWIST and SNAIL levels. We further validated that LINC00968 localized in cytoplasma and acted as an upstream of microRNA miR-22-5p, which was up-regulated in LUAD tissues and cell lines. Besides, elevated miR-22-5p expression abolished the effect of LINC00968 over-expression on LUAD progression including in vivo tumor growth. In addition, we first validated that cell division cycle 14A (CDC14A), which was down-regulated in LUAD tissues, was a downstream target of miR-22-5p. We over-expressed CDC14A in LUAD cells and miR-22-5p induced LUAD progression was partially reversed. Conclusion our study demonstrated that LINC00968 inhibited proliferation, migration and invasion of LUAD by sponging miR-22-5p and further restoring CDC14A. This novel regulatory network might provide us with promising diagnostic and therapeutic target in LUAD treatment.