Objective To screen the lapatinib resistance-related hub genes of breast cancer by bioinformatics initially in order to lay the foundation for further study. Methods We screened and downloaded the gene expression profile data of GSE16179 and GSE38376 from the gene expression omnibus (GEO), and used the limma package of R software to identify the differential expressed genes (DEGs) in breast cancer cells. Then we used the DAVID online website for pathway and function enrichment. With the usage of STRING and Cytoscape, the protein-protein interaction network (PPI) was constructed, and the plug-in app MCODE in Cytoscape was applied to screen hub genes. Then we performed the function enrichment and co-expression analysis of hub genes by DAVID and GeneMANIA. Kaplan-Meier Plotter was used to conduct survival analysis of hub genes. Results A total of 206 kinds of DEGs were screened, and there were 126 kinds of up-regulated genes and 80 kinds of down-regulated genes. DAVID results showed that DEGs were mainly enriched in the biological processes of extracellular space and extracellular region, including extracellular matrix organization, oxygen binding, integrin binding, cell adhesion, positive regulation of angiogenesis, Hippo signaling pathway, transforming growth factor-β signaling pathway and so on. PPI network visualized 74 nodes, the top 10 kinds of hub genes with high connectivity in the gene expression network were screened by MCODE. The Kaplan-Meier Plotter analysis confirmed that 6 of the 10 kinds of hub genes, including peroxisome proliferator activated receptor gamma, transforming growth factor beta receptor 2, tissue inhibitor of metalloproteinase 1, transforming growth factor beta induced, serpin family E member 1, and thrombospondin 1, were correlated with the prognosis of breast cancer patients. Conclusion This 6 kinds of genes may play a significant role in lapatinib resistance of breast cancer.
Objective To observe the effect of forkhead box Q1(FOXQ1) short hairpin RNA (shRNA) on sensitivity of oxaliplatin chemotherapy in hepatpcellular carcinoma cell line SMMC-7721. Methods ① Complementary shRNA oligonucleotides targeting the FOXQ1 gene and negative control-shRNA were designed and inserted into lentiviral vector. shRNA lentivirus vectors were transfected into SMMC-7721 cells and the lentivirus vector with the best silencing effect was screened. ② SMMC-7721 cells were divided into interference group (SMMC-7721 cells were transfected with FOXQ1-shRNA-1), negative control group (SMMC-7721 cells were transfected with negative control-shRNA), and blank control group (SMMC-7721 cells did not received any treatment), and the expressions of FOXQ1 mRNA and its protein in SMMC-7721 cells were detected at 72 hours after transfection. ③ SMMC-7721 cells were divided into interference group, negative control group, blank control group, interference+oxaliplatin group, negative control+oxaliplatin group, and blank control+oxaliplatin group, apoptosis rates and viability of SMMC-7721 cells were detected at 48 hours after transfection. Results ① The expressions of FOXQ1 mRNA and its protein in SMMC-7721 cells of the FOXQ1-shRNA-1 group were both lower than those of the FOXQ1-shRNA-2 group and FOXQ1-shRNA-3 group (P<0.05), so the FOXQ1-shRNA-1 was the best lentiviral vector. ② Compared with the negative control group and the blank control group, the expressions of FOXQ1 mRNA and its protein of the interference group were both lower (P<0.05), but there was no significant difference between the negative control group and the blank control group (P>0.05). ③ Whether added oxaliplatin or not, compared with the negative control group and the blank control group, the apoptosis rates of the interference group were higher (P<0.05), but the viability of the interference group was lower (P<0.05), and there was no significant difference between the negative control group and the blank control group under the same condition (P>0.05). The apoptosis rates of groups (including the interference group, the negative control group, and the blank control group) which added oxaliplatin were higher than those groups didn’t add oxaliplatin (P<0.05), but viability of groups (including the interference group, the negative control group, and the blank control group) which added oxaliplatin was lower than those groups didn’t add oxaliplatin (P<0.05). Conclusion Down-regulation of expression of FOXQ1 by shRNA in hepatocellular carcinoma cell line SMMC-7721 can effectively induce apoptosis and increase sensitivity of SMMC-7721 cells to oxaliplatin.