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Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is known to induce cell apoptosis in many types of cancer cells. However, some malignant cells still exhibit anti‑apoptosis features induced by TRAIL; thus the underlying mechanisms that regulate sensitivity and resistance of tumor cells to TRAIL‑induced apoptosis remain unclear. Human telomerase reverse transcriptase (hTERT) is overexpressed in most types of human tumors and is mostly inactive in somatic cells. The present study aimed to investigate the endogenous effects and mechanisms of hTERT inhibition and TRAIL overexpression on TRAIL‑induced apoptosis of human oral squamous cell carcinoma (OSCC) cells. The effects of adeno‑associated virus (AAV)‑mediated TRAIL and hTERT gene silencing by RNA interference were investigated on the proliferation and apoptosis of human OSCC cells in vitro and in vivo. The present results suggest that knockdown of hTERT expression accelerated TRAIL‑resistant OSCC cells to TRAIL‑induced apoptosis and impaired OSCC cell proliferation. In addition, this process is accompanied by the upregulation of caspase‑3, caspase‑8 and caspase‑9, and downregulation of B cell lymphoma‑2. Additionally, the possible mechanisms underlying the association between TRAIL expression and hTERT silencing were explored. The results demonstrated that TRAIL expression levels were elevated when the hTERT gene was silenced, and notable anti‑tumor effects were observed when TRAIL upregulation and hTERT gene silencing were carried out simultaneously. The present findings provide experimental evidence for the combined use of TRAIL and hTERT as a possible gene therapy strategy in oral cancer.

Sex determining region Y‑box 18 (SOX18) has been found to be overexpressed in several types of tumor. However, the molecular mechanism underlying the biological function of SOX18 in osteosarcoma remains to be elucidated. The present study aimed to elucidate the roles of SOX18 in regulating the biological behavior of osteosarcoma cells. First, SOX18 mRNA expression was analyzed in osteosarcoma tissues using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The results demonstrated that the expression of SOX18 was elevated in osteosarcoma tissue, compared with normal bone tissue. In addition, the knockdown of SOX18 in U2OS or MG63 osteosarcoma cells inhibited cell proliferation and significantly increased the population of cells in the S‑phase of the cell cycle, as measured by the CCK‑8 assay and flow cytometric analysis, respectively. Additionally, suppression of the expression of SOX18 in the osteosarcoma cells significantly induced cell apoptosis as evaluated by annexin V/propidium iodide staining and flow cytometric analysis. The downregulation of SOX18 was found to significantly inhibit cell adhesion and invasion. The mRNA and protein expression levels of transforming growth factor‑β, platelet‑derived growth factor (PDGF)‑A, PDGF‑B and RhoA were also reduced by SOX18 silencing, as assessed by RT‑qPCR and western blot analysis, respectively. These results indicated that SOX18 may function as an oncogene, and may provide a novel and promising therapeutic strategy for osteosarcoma.

To investigate the apoptotic mechanism of triple-negative breast cancer (TNBC) cells induced by gefitinib and PI3K inhibitor SF1126. MDA-MB-231, MDA-MB-436, and MCF-7 cells were incubated with 0.1 μmol/l gefitinib, 1 μmol/l gefitinib, 10 μmol/l gefitinib, 1 μmol/l SF1126, 0.1 μmol/l gefitinib+1 μmol/l SF1126, 1 μmol/l gefitinib+1 μmol/l SF1126, and 10 μmol/l gefitinib+1 μmol/l SF1126. Then, cell viability and survival were determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining. The apoptosis-related factors and phosphoinositide-3-kinase/protein kinase B, the mammalian target of rapamycin (PI3K/AKT-mTOR) signaling pathway-related factors were detected by western blot. For TNBC cells, cell viability or survival was not significantly inhibited by gefitinib or SF1126 alone; however, marked cell apoptosis was noted in the gefitinib and SF1126 combination groups, and this effect was dose dependent. Also, the expressions of apoptosis markers, such as cleaved caspase-3, Bcl-2/Bax, were altered by the gefitinib and SF1126 combination. Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6-kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination, which may be responsible for the apoptosis. Gefitinib combined with SF1126 could induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR-PI3K-AKT-mTOR-p70S6K pathway. Our studies have set the stage for future clinical trials of TNBC therapy by the combination of gefitinib and SF1126.

Objective: To investigate the effect of long intergene non-coding RNA 00519 (LINC00519) on the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by regulating the miR-876-3p / high mobility group protein A1 (HMGA1) axis. Methods: The expression levels of LINC00519 in gastric cancer HGC-27 cells and gastric mucosal epithelial GES-1 cells were detected by qPCR. HGC-27 cells were divided into si-NC, si-LINC00519, si-LINC00519+anti-miR-NC, and si-LINC00519 + anti-miR-876-3p groups according to transfection treatment. Colony formation test was applied to detect cell cloning ability; Flow cytometry was used to detect apoptosis and cell cycle distribution; Transwell assay was selected to measure cell migration and invasion. Dual luciferase reporter gene assay and qPCR were applied to confirm the interaction between LINC00519 and miR-876-3p as well as between miR-876-3p and HMGA1. Results: The expression of LINC00519 in HGC-27 cells was significantly higher than that in GES-1 cells (P<0.05). After siRNA transfection, the expression level of LINC00519 in HGC-27 cells of the si-LINC00519 group was significantly lower than that of the si-NC group (t=47.294, P<0.01). Compared with the si-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, and proportion of S-phase cells in the si-LINC00519 group were significantly decreased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells were significantly increased (all P<0.01). Compared with the si-LINC00519+anti-miR-NC group, the number of HGC-27 cell clones, the number of migrated and invaded cells, proportion of S-phase cells were significantly increased (all P<0.01), while the apoptosis rate and the proportion of G0/G1 phase cells in the si-LINC00519 + anti-miR-876-3p group were significantly decreased (all P<0.01). LINC00519 could target and negatively regulate miR-876-3p expression. miR-876-3p could target and negatively regulate HMGA1 expression. Conclusion: Knocking down LINC00519 could inhibit the proliferation, migration and invasion of gastric cancer HGC-27 cells and induce apoptosis by regulating the miR-876-3p/HMGA1 axis. [ABSTRACT FROM AUTHOR]