Effect of miR-21 on Apoptosis in Lung Cancer Cell Through Inhibiting the PI3K/ Akt/NF-κB Signaling Pathway in Vitro and in Vivo

Abstract

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.

microRNA-21 upregulates YAP by inhibiting transcription factor RUNX1 to regulate immunosuppressive ability of myeloid-derived suppressor cells in lung cancer

“…Overexpression of miR-21-5p by mesenchymal stem cell-secreted extracellular vesicles (MSC-EVs) promotes lung cancer development [8]. Moreover, suppressing miR-21 inhibits cell migration and invasion in non-small cell lung carcinoma (NSCLC) cells [9]. In the current study, microarray-based analysis predicted RUNX1 to be one of the downstream target genes by miR-21.…”

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

“…These pathways may be the major factor for fucosterol's resistance to non-small cell lung cancer, such as PI3K-Akt signaling pathway, VEGF signaling pathway, ErbB signaling pathway. The PI3K-Akt signaling pathway is widely recognized as a prominent cancer signaling pathway, which is closely related to affect the proliferation, survival and apoptosis of NSCLC cells [32][33][34]. Also, VEGF signaling pathway involves in tumor cell-dependent continuous vascular supply, which has a profound effect on tumor cell growth and metastasis [35].…”

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer based on network pharmacology and molecular docking

“…These pathways may be the major factor for fucosterol's resistance to non-small cell lung cancer, such as PI3K-Akt signaling pathway, VEGF signaling pathway, ErbB signaling pathway. The PI3K-Akt signaling pathway is widely recognized as a prominent cancer signaling pathway, which is closely related to affect the proliferation, survival and apoptosis of NSCLC cells [32][33][34]. Also, VEGF signaling pathway involves in tumor celldependent continuous vascular supply, which has a profound effect on tumor cell growth and metastasis [35].…”