Long noncoding RNAs (lncRNAs) have been illustrated as vital molecules in regulating human cancer by emerging evidence. LINC00163 is a novel lncRNA without functional definition. In this study, we investigated its role in the tumorigenesis of lung cancer. The results showed that LINC00163 level was significantly downregulated in lung cancer tissues and cell lines by bioinformatics and qRT-PCR analyses. Notably, we observed that LINC00163 expression was lower in metastatic tissues than in non-metastatic cases. Furthermore, higher expression of LINC00163 in patients with lung cancer predicted better prognosis. Gain-of-function assays illustrated that upregulation of LINC00163 dramatically suppressed the proliferation, migration and invasion of lung cancer cells <i>in vitro</i>, whereas promoting apoptosis. Consistently, LINC00163 overexpression impaired tumor propagation <i>in vivo</i>. Mechanical study revealed that LINC00163 recruited ARID1A to the promoter of TCF21 and initiated its expression. In conclusion, we concluded that LINC00163/ARID1A/TCF21 regulatory loop modulated the development of lung cancer, providing a new insight on the mechanism underlying lung cancer progression.
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