Background/Aims: Lung cancer is one of the most common malignancies in the world. Apoptosis-stimulating protein of p53 (ASPP2), a tumorigenesis related protein, plays a critical role in the initiation and development of various types of cancers. However, the effect of ASPP2 on lung cancer remains unknown. The purpose of this study aims to investigate the mechanism of ASPP2 regulated by miR-21 in lung cancer in vitro and in vivo. Methods: In the study, migration and invasion assays, apoptosis assay, caspase activity assay, TUNEL staining, real time PCR and western blot were used to investigate the mechanism of ASPP2 regulated by miR-21 in lung cancer in vitro and in vivo. Results: We demonstrated that the miR-21 inhibitor induced apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in non-small cell lung carcinoma (NSCLC). Moreover, ASPP2 was directly targeted by miR-21 in NSCLC cells. Down-regulation of miR-21 suppressed cell migration and invasion, as well as the EMT signaling pathway in NSCLC cells. Furthermore, the miR-21 inhibitor induced cell apoptosis via the caspase dependent pathway in NSCLC cells. The miR-21 inhibitor enhanced caspase-3, 8, 9 activity in NSCLC cells. In addition, the caspase inhibitor significantly reduced the apoptosis induced by the miR-21 inhibitor in NSCLC cells. Conclusions: Our results revealed that the miR-21 inhibitor could induce apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in human NSCLC cells, and might serve as a therapeutic strategy to treat NSCLC.
Background Lung cancer is one of the most common malignant tumors worldwide. CD36 is a receptor for fatty acids and plays an important role in regulating fatty acid metabolism, which is closely related to tumorigenesis and development. The regulation of miR-21 and its role in tumorigenesis have been extensively studied in recent years. However, the relationship between miR-21 and CD36 regulated fatty acid metabolism in human non-small cell lung cancer remains unknown. Methods In this study, lentivirus transfection, qRT-PCR, cell migration, immunofluorescence, and western blot were used to examine the relationship between miR-21 and CD36 regulated fatty acid metabolism and the regulation role of miR-21 in human non-small cell lung cancer. Results This study demonstrated that up-regulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells. Moreover, the intracellular contents of lipids including cellular content of phospholipids, neutral lipids content, cellular content of triglycerides were significantly increased following miR-21 mimic treatment compared with control, and the levels of key lipid metabolic enzymes FASN, ACC1 and FABP5 were obviously enhanced in human non-small cell lung cancer cells. Furthermore, down-regulation of CD36 suppressed miR-21 regulated cell growth, migration and intracellular contents of lipids in human non-small cell lung cancer cells, which suggested that miR-21 promoted cell growth and migration of human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism. Inhibition of miR-21 was revealed to inhibit cell growth, migration, intracellular contents of lipids, and CD36 protein expression level in human non-small cell lung cancer cells. In addition, PPARGC1B was a direct target of miR-21, and down-regulation of PPARGC1B reversed the inhibition of CD36 expression induced by miR-21 inhibitor. Conclusions These results explored the mechanism of miR-21 promoted non-small cell lung cancer and might provide a novel therapeutic method in treating non-small cell lung cancer in clinic.
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