RESUMEN
The role of ROR1-AS1 in non-small-cell lung cancer (NSCLC) remains unclear. Therefore, we aimed to investigate the functional role of ROR1-AS1 in NSCLC and to explore the underlying mechanisms. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was performed to detect cell proliferation. Transwell assay was performed to evaluate cell invasive ability. Cell apoptotic rates and caspase-3/7 activity were determined to evaluate apoptosis. The expression levels of PI3K/Akt/mTOR pathway-related proteins were measured using Western blot analysis. Results showed that ROR1-AS1 expression was upregulated in NSCLC samples. Knockdown of ROR1-AS1 inhibited the viability and invasive ability of NSCLC cells. Knockdown of ROR1-AS1 induced apoptotic rate and caspase-3/7 activity and suppressed xenograft NSCLC tumor growth. In addition, ROR1-AS1 knockdown inhibited the activation of the PI3K/Akt/mTOR pathway in NSCLC cells. However, treatment with 740Y-P prevented the effects of si-ROR1-AS1 on viability, invasive ability, and apoptosis of NSCLC cells. These findings implied that ROR1-AS1 played an oncogenic role in NSCLC via regulating the PI3K/Akt/mTOR pathway.
Asunto(s)
Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/metabolismo , ARN Neoplásico/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Serina-Treonina Quinasas TOR/genéticaRESUMEN
Increasing studies have well-documented the involvement of numerous lncRNAs in regulating the malignant phenotypes of various tumors including non-small cell lung cancer (NSCLC) cells. However, up to date, the effects and mechanism of lncRNA amine oxidase, copper containing 4, pseudogene (AOC4P) in NSCLC progression remain undefined. AOC4P expression in NSCLC cells was detected by qRT-PCR. The protein levels of Wnt/ß-catenin pathway-related proteins, matrix metallopeptidase (MMP)-2, and MMP-9 were examined by Western blot. The effects of AOC4P or combined with Wnt agonist BML-284 on the malignant phenotypes in NSCLC cells were explored by CCK-8, Transwell invasion assay, flow cytometry analysis and caspase-3/7 activity. AOC4P was lowly expressed in NSCLC samples and cells. Overexpression of AOC4P inhibited viability, the expression of MMP-2 and MMP-9, and invasion of NSCLC cells. Apoptosis and caspase-3/7 activity were suppressed in response to AOC4P overexpression in NSCLC cells. AOC4P overexpression suppressed tumor growth in a xenograft mouse model. Activation of the Wnt/ß-catenin pathway by BML-284 abolished the effects of AOC4P overexpression on cell viability, invasion and apoptosis in NSCLC cells. In conclusion, AOC4P overexpression suppresses viability and invasion and induces apoptosis in NSCLC cells via inhibition of the Wnt/ß-catenin pathway.
