Long noncoding RNAs (lncRNAs) play crucial roles in the acquired resistance to EGFR-directed therapies in lung cancer. LncRNA OSER1-AS1 has been reported to promote tumorigenesis of hepatocellular carcinoma. However, its functions and underlying molecular mechanisms remain unclear in the acquired gefitinib-resistance of lung cancer. Our study revealed that increased expression of OSER1-AS1 was correlated with gefitinib resistance in lung adenocarcinoma. Higher OSER1-AS1 expression predicted disease progression of lung adenocarcinoma patients. The in vitro assays indicated OSER1-AS1 contributed to gefitinib resistance of lung adenocarcinoma cells via inhibiting cell apoptosis and cell cycle arrest. In vivo experiments showed that the knockdown of OSER1-AS1 restored the sensitivity of lung cancer cells to gefitinib. Further studies showed that OSER1-AS1 functioned as a molecular sponge of miR-612. OSER1-AS1 down-regulated miR-612 to increase FOXM1 expression, suggesting that miR-612/FOXM1 axis was regulated by OSER1-AS1, which was partially responsible for gefitinib resistance of lung adenocarcinoma. In conclusion, OSER1-AS1 promoted gefitinib resistance of lung adenocarcinoma through the miR-612/FOXM1 axis.
Keywords: FOXM1; LncRNA OSER1-AS1; gefitinib; lung adenocarcinoma; miR-612.
AJTR Copyright © 2021.