RESUMEN
The present study aimed to identify genes associated with tongue cancer in patients with a history of tobacco and/or alcohol use. Microarray dataset GSE42023, including 10 tissue samples of tongue cancer from patients with a history of tobacco and/or alcohol use (habit group) and 11 tissue samples of non-habit-associated tongue cancer (non-habit group), were downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) between the habit and non-habit groups were identified using the Linear Models for Microarray Data software package. The enrichment functions and pathways of these genes were subsequently predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Transcription factors (TFs) and tumor-associated genes (TAGs) were selected from the DEGs using the Encyclopedia of DNA Elements database and the TAG database, respectively. Protein-protein interaction (PPI) networks for DEGs were constructed using Cytoscape. In addition, functional module analysis was performed using BioNet. This analysis identified 642 DEGs between the habit and non-habit groups, including 200 upregulated and 442 downregulated genes. The majority of upregulated DEGs were functionally enriched in the regulation of apoptosis and the calcium signaling pathway. The majority of downregulated DEGs were functionally enriched in fat cell differentiation and the adipocytokine signaling pathway. In addition, 31 TFs and 42 TAGs were identified from the DEGs. Furthermore, this analysis demonstrated that certain DEGs, including AKT serine/threonine kinase 1 (AKT1), E1A binding protein p300 (EP300), erb-b2 receptor tyrosine kinase 2 (ERBB2) and epiregulin (EREG), had high connectivity degrees in the PPI networks and/or functional modules. Overall, DEGs in a functional module, such as AKT1, EP300, ERBB2 and EREG, may serve important roles in the development of tongue cancer in patients with a history of tobacco and/or alcohol use. These DEGs are potential therapeutic targets for the treatment of tongue cancer in these groups.
RESUMEN
OBJECTIVE: To study the effect of silencing survivin on the growth of Hep-2 human laryngeal cancer cells in vitro and in vivo. METHODS: Hep-2 cells were transfected with pGCsilencer-siRNA-survivin (psi-survivin)by Lipofectamine 2000. The mRNA and protein expressions of survivin were detected by semi-quantitative RT-PCR and Western blot, respectively. Cell proliferation activity was measured by MTT assay. Apoptosis was assessed by flow cytometry. The implanted tumors were formed from injected Hep-2 cells in nude mice. After the tumor formation, psi-survivin was injected into peritumor tissues. The growth of tumor were observed. The tumor volume was calculated and the tumor growth curve was plotted. The expression of survivin in tumor tissues was detected by Western blot. The tumor cell apoptosis was observed by Tunel staining. RESULTS: The sequence-specific siRNA of survivin inhibited the expressions of survivin mRNA and protein. The inhibition rates of survivin mRNA and protein expression were 54.4% and 37.0% respectively. Also the growth of Hep-2 cells was inhibited significantly, with a decrease by 71.7%. By the day 32 of tumor growth, the mean tumor volumes were (1443.9 ± 230.5) mm(3) (x(-) ± s) in saline control group, (1348.5 ± 198.4) mm(3) in plasmid-negative control group, and (624.6 ± 188.4) mm(3) in psi-survivin group, respectively (t = -5.917, P < 0.01). In the implanted tumors injected with psi-survivin, survivin protein expression was down-regulated significantly, with a inhibition rate of 41.8%. Tunel staining showed the apoptosis occurred in the implanted tumors. CONCLUSION: Silencing survivin could significantly inhibit the growth of Hep-2 human laryngeal cancer cells in vitro and in vivo.