Twist1-mediated 4E-BP1 regulation through mTOR in non-small cell lung cancer
PUBLISHED: 2015-11-26  361 total views, 1 today

Tangfeng Lv1  QianWang2  Yong Song3  Weimin Gao4

1Jiangsu, China Jinling Hospital,NanjingDepartment of Respiratory Medicine. 2Nanjing, China Jiangsu Province Hospital ofChinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Respiratory Medicine. 3Nanjing, China Jinling Hospital,NanjingDepartment of Respiratory Medicine. 4Department of Environmental Toxicology


ObjectiveTwist1over expression has been reported to correspond with poorsurvival in non-smallcell lung cancer (NSCLC), but the underlining mechanismis not clear. Theobjective of the present study was to investigate thetumorigenic role of Twist1and its related molecular mechanisms in NSCLC. Twist1 was over expressed in34.7% NSCLC patients. The survival rate was significantly lower in patientswith high Twist1 expression than those with low expression (P<0.05).Twist1 expression levels were higher in H1650 cells, but relatively lower inH1975 cells. H1650 cells with stable Twist1 knockdown, H1650shTw, demonstrateda significantly slower rate of wound closure; however, H1975 cells with stableTwist1 over expression, H1975 Over, had an increased motility velocity. Asignificant decrease in colony number and size was observed in H1650shTw cell, buta significant increase in colony number was found in H1975 Over cells. Tumorgrowth significantly decreased in mice implanted with H1650shTw cells comparedto H1650 cells (P<0.05). 4E-BP1 and p53 gene expressions were increase,but p-4E-BP1 and p-mTOR protein expressions weredecreased in H1650shTw cells. p-4E-BP1was over expressed in 24.0% NSCLC patients. The survival rate was significantlylower in patients with high p-4E-BP1 expression than those with low p-4E-BP1 (P<0.01).A significant correlation was found between Twist1 and p-4E-BP1 (P<0.01).A total of 13genes in RT-PCR array showed significant changes in H1650shTwcells. Altogether, Twist1 is correlated with 4E-BP1 in predicting theprognostic outcome of NSCLC. Inhibition of Twist1 decreases p-4E-BP1 expressionpossibly through downregulating p-mTOR and increasing p53 expression in NSCLC. MethodTwist1over expression has been reported to correspond with poorsurvival in non-smallcell lung cancer (NSCLC), but the underlining mechanismis not clear. Theobjective of the present study was to investigate the tumorigenic role ofTwist1 and its related molecular mechanisms in NSCLC. Twist1 was over expressedin 34.7% NSCLC patients. The survival rate was significantly lower in patientswith high Twist1 expression than those with low expression (P<0.05).Twist1 expression levels were higher in H1650 cell, but relatively lower inH1975 cells. H1650 cells with stable Twist1 knock dow, H1650shTw, demonstrateda significantly slower rate of wound closure; howeve, H1975 cells with stableTwist1 overexpression, H1975Over, had an increased motilityvelocity. A significantdecrease in colony number and size was observed in H1650shTw cells, but asignificant increase in colony number was found in H1975 Over cells. Tumorgrowth significantly decreased in mice implanted with H1650shTw cells comparedto H1650 cells (P<0.05). 4E-BP1 and p53 gene expressions wereincreased, but p-4E-BP1 and p-mTOR protein expressions were decreased inH1650shTw cells. p-4E-BP1 was over expressed in 24.0% NSCLC patients. Thesurvival rate was significantly lower in patients with highp-4E-BP1 expressionthan those with low p-4E-BP1 (P<0.01). A significant correlation wasfound between Twist1 and p-4E-BP1 (P<0.01). A total of 13 genes inRT-PCR array showed significant changes in H1650shTw cells. Altogether, Twist1is correlated with 4E-BP1 in predicting the prognostic outcome of NSCLC.Inhibition of Twist1 decreases p-4E-BP1 expression possiblythroughdownregulating p-mTOR and increasing p53 expression in NSCLC. ResultTwist1over expression has been reported to correspond with poorsurvival innon-smallcell lung cancer (NSCLC), but the underlining mechanismis not clear. Theobjective of the present study was to investigate the tumorigenic role ofTwist1 and its related molecular mechanisms in NSCLC. Twist1 was over expressedin 34.7% NSCLC patients. The survival rate was significantly lower in patientswith high Twist1 expression than those with low expression (P<0.05).Twist1 expression levels were higher in H1650 cell, but relatively lower inH1975 cells. H1650 cells with stable Twist1 knockdow, H1650shTw, demonstrated asignificantly slower rate of wound closure; howeve, H1975 cells with stableTwist1 over expression, H1975Over, had an increased motilityvelocity. A significantdecrease in colony number and size was observed in H1650shTw cells, but asignificant increase in colony number was found in H1975Over cells. Tumorgrowth significantly decreased in mice implanted with H1650shTw cells comparedto H1650 cells (P<0.05). 4E-BP1 and p53 gene expressions wereincreased, but p-4E-BP1 and p-mTOR protein expressions were decreased inH1650shTw cells. p-4E-BP1 was over expressed in 24.0% NSCLC patients. Thesurvival rate was significantly lower in patients with highp-4E-BP1 expressionthan those with low p-4E-BP1 (P<0.01). A significant correlation wasfound between Twist1 and p-4E-BP1 (P<0.01). A total of 13 genes inRT-PCR array showed significant changes in H1650shTw cells. Altogether, Twist1is correlated with 4E-BP1 in predicting the prognosticoutcome of NSCLC.Inhibition of Twist1 decreases p-4E-BP1 expression possibly through down regulatingp-mTOR and increasing p53 expression in NSCLC. ConclusionTwist1over expression has been reported to correspond with poorsurvival in non-smallcell lung cancer (NSCLC), but the underlining mechanismis not clear. Theobjective of the present study was to investigate the tumorigenic role ofTwist1 and its related molecular mechanisms in NSCLC. Twist1 was over expressedin34.7% NSCLC patients. The survival rate was significantly lower in patientswith high Twist1 expression than those with low expression (P<0.05).Twist1 expression levels were higher in H1650 cell, but relatively lower inH1975 cells. H1650 cells with stable Twist1 knockdown, H1650shTw, demonstrateda significantly slower rate of wound closure; however, H1975 cells with stableTwist1 over expression, H1975Over, had an increased motilityvelocity. A significantdecrease in colony number and size was observed in H1650shTw cells, but asignificant increase in colony number was found in H1975Over cells. Tumorgrowth significantly decreased in mice implanted with H1650shTw cells comparedto H1650 cells (P<0.05). 4E-BP1 and p53 gene expressions wereincreased, but p-4E-BP1 and p-mTOR protein expressions were decreased inH1650shTw cells. p-4E-BP1 was over expressed in 24.0% NSCLC patients. Thesurvival rate was significantly lower in patients with highp-4E-BP1 expressionthan those with low p-4E-BP1 (P<0.01). A significant correlation wasfound between Twist1 and p-4E-BP1 (P<0.01). A total of 13 genes inRT-PCR array showed significant changes in H1650shTw cells. Altogether, Twist1is correlated with 4E-BP1 in predicting the prognostic outcome of NSCLC.Inhibition of Twist1 decreases p-4E-BP1 expression possiblythroughdownregulating p-mTOR and increasing p53 expression in NSCLC.


KeywordsTwist1


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