Background
Lung cancer is the leading cause of cancer-related mortality worldwide. Studies have demonstrated that long noncoding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) functioned as an oncogene in most malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the underlying mechanisms of NNT-AS1 in NSCLC progression.
Conclusion
NNT-AS1 facilitated proliferation, migration, invasion and EMT of NSCLC cells by sponging miR-22-3p and regulating YAP1 expression, which might provide a potential biomarker and therapeutic target for NSCLC.
Methods
The levels of NNT-AS1, miR-22-3p and Yes-associated protein (YAP1) were detected by qRT-PCR in NSCLC tissues and cells. Kaplan-Meier analysis was conducted to analyze the correlation between NNT-AS1 expression and overall survival of NSCLC patients. Cell proliferation was evaluated by MTT assay. Cell migration and invasion were assessed using transwell assay. The protein levels of YAP1 and EMT-related proteins were detected by western blot. The molecular mechanism was predicted by starBase2.0 and validated by dual-luciferase reporter assay or RNA pull-down assay. Xenograft analysis was carried out to analyze tumor growth in vivo.
Results
We found that the levels of NNT-AS1 and YAP1 were enhanced, while miR-22-3p expression was decreased in NSCLC tissues and cells. High NNT-AS1 expression was correlated with poor prognosis. NNT-AS1 knockdown impeded proliferation, migration, invasion and EMT of NSCLC cells. NNT-AS1 targeted miR-22-3p, and YAP1 was a target of miR-22-3p in NSCLC cells. Furthermore, NNT-AS1 facilitated the progression of NSCLC by regulating miR-22-3p/YAP1 axis. NNT-AS1 knockdown repressed tumor growth in vivo.