Abstract. Human securin, encoded by pituitary tumor transforming gene 1, is implicated in several oncogenic processes in the pathogenesis of brain tumors, including glioma. The aim of the present study was to examine the effect of securin on the migration and invasion of glioma cells. The results revealed that the overexpression of securin in glioma LN-229 cells significantly increased the invasion and transmigration abilities. By contrast, these abilities were significantly reduced by the downregulation of securin in glioma U373 cells. Furthermore, the results demonstrated that securin overexpression and downregulation significantly increased and decreased the levels of matrix metalloproteinase 2 and 9, respectively. These findings indicate a promotive role for securin in glioma migration and invasion, which may involve the action of matrix metalloproteinases.

miR-655-3p functions as a tumor suppressor in tumor metastases; however, its role and mechanism in regulating cell migration and invasion of non-small cell lung cancer (NSCLC) remain unclear. Here, we found that miR-655-3p expression was markedly decreased in the NSCLC cell lines A549, NCI-H1650, PC14/b, NCI-H1299, and HPAEpiC compared to levels observed in normal human lung fibroblasts. miR-655-3p overexpression significantly inhibited migration and invasion of A549 and PC14/b cells, and pituitary tumor-transforming 1 (PTTG1) expression was up-regulated in the NSCLC cells. Luciferase reporter assays indicated that PTTG1 was a direct target of miR-655-3p. Additionally, PTTG1 overexpression alleviated the inhibitory effect of miR-655-3p on migration and invasion abilities in A549 and PC14/b cells. In conclusion, miR-655-3p inhibits NSCLC migration and invasion by targeting PTTG1, suggesting that miR-655-3p may serve as a therapeutic target to provide a new approach for the clinical treatment of NSCLC.

Purpose: DANCR plays an important role in various types of cancer. However, its role in gliomas remains unclear. In the present study, we aimed to investigate the mechanism underlying the role of DANCR in gliomas. Methods: DANCR expression was measured by qRT-PCR, and expression of LGR5, PI3K, AKT, and phosphorylated AKT (p-AKT) was detected by western blotting. The combination of miR-216a and DANCR was quantified by Luciferase reporter assays. Proliferation, apoptosis and cell cycle, migration and invasion, and angiogenesis of glioma cells were measured by MTT, flow cytometry, Transwell, and Tube formation assays, respectively. Results: DANCR expression was significantly higher in glioma cells than in normal human astrocytes. Silencing of DANCR inhibited proliferation, migration, invasion, and angiogenesis of glioma cells, promoted apoptosis, blocked the cell cycle at the G1/S transition, and reduced LGR5, PI3K, and p-AKT expression. We identified miR-216a as a direct target of DANCR. Silencing of DANCR in glioma cells increased miR-216a expression. Further, miR-216a suppression increased proliferation, migration, invasion, and angiogenesis and inhibited apoptosis of glioma cells transfected with DANCR-targeting siRNA. In addition, miR-216a suppression compromised inhibition of the G1/S transition caused by DANCR silencing. Furthermore, suppression of miR-216a increased accumulation of LGR5, PI3K, AKT, and p-AKT in glioma cells transfected with DANCR-targeting siRNA. Conclusion: DANCR modulates growth and metastasis by targeting the miR-216a/LGR5 axis and PI3K/AKT signaling pathway.

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. Leptin is a pleiotropic hormone with antiapoptotic and proliferative roles involved in several systems. However, there is no known antiapoptotic mechanism of leptin in non-small cell lung cancer (NSCLC). So, we investigated the antiapoptotic mechanism of leptin in NSCLC. Proliferation, apoptosis, and the specific mechanism of leptin-transfected cells were analyzed in this study. Leptin, p-Perk, IRE1, cleaved ATF6, spliced XBP1, eIF2-α, TRAF2, CHOP, and caspase 12 proteins were detected by Western blot, and endoplasmic reticulum (ER) stress-related mRNA was detected by semi-quantitative reverse transcription PCR (RT-PCR). Leptin in A549 and transfected cells inhibited cisplatin-activated ER stress-associated mRNA transcription and activation of proteins. ER stress unfolded protein response (UPR) proteins, PERK and ATF6, were involved in leptin-triggered apoptosis. XBP1 and TRAF2 were increased significantly when treated with cisplatin in A549-siLPT and non-transfected cells. CHOP expression was blocked in A549 and transfected cells (LPT-PeP and LPT-EX cells). In conclusion, leptin can promote the proliferation of A549 cells through blocking ER stress-mediated apoptosis. This blocking is mediated by the p-Perk and ATF6 pathway through blocking activation of CHOP.