ABSTRACT
Objective To explore the expression and clinical pathological significance of long non-coding transcription factor 7 (lncTCF7) in gastric cancer tissues and to investigate the role of lncTCF7 in the invasion and metastasis of gastric cancer by in vitro experimental study.Methods From January to June 2011,one hundred patients with gastric cancer who underwent radical gastrectomy were selected from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.The expression of lncTCF7 at mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR).The patients were divided into high expression group (50 cases) and low expression group (50 cases) according to the lncTCF7 mRNA expression level.The stable interferenced lncTCF7 cell line (stable interference group) and blank control lncTCF7 cell line (blank control group) were established.Then the relationship between lncTCF7 expression level and clinical pathological characteristics and prognosis was analyzed.The interferenced lncTCF7 cell line was constructed and utilized,and the role of lncTCF7 in the invasion and metastasis of gastric cancer was detected by wound healing,Transwell and Western blotting method.The Chi square test and t test were performed for statistical analysis.The Kaplan-Meier curve was used for survival analysis.Univariate and multivariate analyses were used for screening the independent factors affecting prognosis.Results The results of qRT-PCR showed that the expression levels of lncTCF7 mRNA in high expression group and low expression group were 0.019 ± 0.003 and 0.002 ± 0.001,respectively.The survival rate of high expression group was lower than that of low expression group (46％,23/50 vs.72％,36/50),and the difference was statistically significant (P =0.002 5).The expression level of lncTCF7 was correlated with intravascular tumor thrombus formation,nerve invasion,depth of invasion and lymph node metastasis (x2 =7.862,7.162,11.903 and 8.280,all P ＜ 0.05).The results of univariate and multivariate analyses showed that the expression level of lncTCF7 was significantly correlated with the depth of invasion (hazard ratio (HR) =4.205,P =0.002;HR =3.125,P =0.018).The results of wound healing assay indicated that lncTCF7 interference could significantly inhibit wound healing ((92.90 ± 1.51) ％ vs.(12.33 ± 0.67) ％,t =48.72,P ＜ 0.01).The results of Transwell assay demonstrated that after 24 hours of culture the number of cells passed through the membrane of the chamber of blank control group was higher than that of stable interference group (83.6 ± 12.5 vs.26.6 ± 4.3),and the difference was statistically significant (t =9.65,P ＜ 0.01).The results of Western blotting showed that the expression of E-cadherin,a marker of epithelial origin,of stable interference group was significantly increased compared with that of blank control group (0.32 ±0.01 vs.0.76 ± 0.01),however the expression levels of vimentin and N-cadherin,markers of mesenchymal origin,were significantly decreased (0.56 ±0.01 vs.0.39 ± 0.01 and 0.67 ± 0.01 vs.0.33 + 0.01),and the differences were all statistically significant (t =26.68,10.09 and 24.14,all P ＜ 0.05).Conclusions The prognosis of gastric cancer patients with high expression of lncTCF7 is poor.lncTCF7 may promote the invasion and metastasis of gastric cancer by influencing eoithelial-mesenchymal transition in gastric cancer cells.
ABSTRACT
DEAD box family,characterized by the conserved motif D (Asp)-E (Glu)-A (Ala)-D (Asp),are putative RNA helicases,which participate in all cellular processes regulated by RNAs.Studies show that there are examples of dysregulation of DDX family expression in various types of cancer.They are involved in the occurrence and evolution of tumor,and take part in tumor cell proliferation,apoptosis,cycle,invasion,metastasis and metabolism,which can be acted as new molecular markers for the diagnosis of tumor,the evaluation of malignancy and the prediction of clinical prognosis and also provide new potential molecular targets for tumor therapy.Here,we reviewed the structure,biochemical function and the relationship with tumor of DDX family.