目的研究ITGA5经RNA干扰后对宫颈癌细胞生长和侵袭的影响。方法应用TNMplot、Kaplan-Meier Plotter、Human Protein Atlas数据库分析ITGA5在宫颈癌中的表达和对患者生存率的影响,采用两条靶向ITGA5的特异siRNA序列,进行RNA干扰实验。实...目的研究ITGA5经RNA干扰后对宫颈癌细胞生长和侵袭的影响。方法应用TNMplot、Kaplan-Meier Plotter、Human Protein Atlas数据库分析ITGA5在宫颈癌中的表达和对患者生存率的影响,采用两条靶向ITGA5的特异siRNA序列,进行RNA干扰实验。实验分为siITGA5#1干扰组、siITGA5#2干扰组和阴性对照组(非特异性siRNA)。实时定量PCR和Western blot法分别检测宫颈癌细胞中ITGA5的mRNA与蛋白水平,筛选内源性ITGA5呈高表达的HeLa及C-33A细胞做后续实验。Western blot法评估siRNA干扰后宫颈癌HeLa/C-33A细胞中ITGA5水平,并先后检测c-Myc、BCL-2、Bax及Vimentin、E-cadherin的表达变化,CCK-8法检测HeLa/C-33A细胞增殖,流式细胞术检测细胞凋亡,Transwell小室侵袭实验评估细胞侵袭能力。结果与阴性对照组相比,特异性siRNA显著下调宫颈癌HeLa/C-33A细胞中ITGA5蛋白的表达;宫颈癌细胞增殖明显受抑,细胞凋亡显著增加(P<0.05);c-Myc和BCL-2表达下降、Bax表达升高。干扰ITGA5后,HeLa/C-33A细胞侵袭能力显著降低,间质性标记物Vimentin的表达明显受抑,上皮细胞标记物E-cadherin表达水平明显增加。结论ITGA5经RNA干扰后,能明显抑制宫颈癌细胞生长和侵袭,ITGA5对宫颈癌细胞侵袭能力的影响可能是通过调控上皮细胞间质化来实现的。展开更多
AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping wa...AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.展开更多
基金Supported by The National R and D Program for Cancer ControlMinistry of Health and Welfare+1 种基金South KoreaNo.1120330
文摘AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.
