Linc00941高表达通过激活TGF-β1/SMAD信号通路促进胃癌的恶性生长

Linc00941 overexpression promotes the malignant growth of gastric cancer by activating TGF-β1/SMAD signaling pathway

目的探究Linc00941对胃癌(GC)的预后影响及其可能机制。方法选取2016年5月至2019年5月于本院住院手术病理为GC的患者91例,按病理分级分为低度恶性组(LGC group,n=31)和高度恶性组(HGC group,n=60)。收集两组受检者的肿瘤组织,并取癌旁5cm以上正常胃组织作为对照组(Control group,n=91),检测Linc00941、转化生长因子-β1(TGF-β1)和SMAD4蛋白的表达水平,分析Linc00941与TGF-β1、SMAD4的关系,并随访患者术后无瘤生存情况,将患者按照Linc00941表达水平分为Linc00941低表达组(LLGC,n=45)和Linc00941高表达组(HLGC,n=46),分析Linc00941表达与临床预后的关系。选取胃癌细胞系HS-746T细胞分为对照组(Sham group)、阴性对照组(NC group)和Linc00941抑制组(Inhibit group),转染Linc00941-inhibitor、Linc00941-NC入HS-746T细胞,分析抑制Linc00941对肿瘤细胞增殖能力、侵袭能力的影响,以及对TGF-β1和SMAD4表达的影响。结果HGC、LGC组的Linc00941、TGF-β1、SMAD4表达水平均高于Control组,且在HGC组的表达水平均高于LGC组(P<0.05);Linc00941表达水平与TGF-β1、SMAD4表达正相关(P<0.05);Linc00941高表达组无瘤生存期低于Linc00941低表达组(P<0.05);抑制Linc00941后HS-746T细胞增殖和侵袭能力较Sham组明显下降,TGF-β1、SMAD4表达明显减少(P<0.05)。结论Linc00941与胃癌恶性度有关,抑制Linc00941后可以通过降低TGF-β1/SMAD4表达减轻胃癌细胞的恶性生长,为胃癌的临床诊断和治疗提供新的依据。

Objective To explore the role of Linc00941 in gastric cancer(GC)and the possible mechanisms.Methods Ninety-one patients with surgical pathology of GC in our hospital from May 2016 to May 2019 were divided into low grade cancer group(LGC,n=31)and high grade cancer group(HGC,n=60)according to pathological classification.Tumor tissues were collected,and adjacent tissues 5 cm above cancer were taken as Control(n=91).Expressions of Linc00941,transforming growth factor-β1(TGF-β1)and SMAD4 proteins were detected and the relationship analyzed.The tumor-free survival was followed up for 2 years after surgery.According to Linc00941 expression level,the patients were divided into Linc00941-low expression group(LLGC,n=45)and Linc00941-high expression group(HLGC,n=46)to analyze the relationship between Linc00941 expression and clinical prognosis.Gastric cancer HS-746T cells were untreated as control group(Sham),transfected with Linc00941-NC(NC),and transfected with Linc00941 inhibitor(Inhibit),respectively,and the effects of inhibiting Linc00941 on proliferation and invasion of tumor cells,the expression of TGF-β1 and SMAD4 were examined.Results Expression levels of Linc00941,TGF-β1 and SMAD4 in HGC and LGC groups were higher than those in Control group,and expression levels in HGC group were higher than those in LGC group(P<0.05).The expression of Linc00941 was positively correlated with TGF-β1 and SMAD4(P<0.05).The tumor-free survival of Linc00941-high expression group was lower than that of Linc00941-low expression group(P<0.05).After Linc00941 inhibition,the proliferation and invasion ability of HS-746T cells were decreased,with decreases in TGF-β1 and SMAD4(P<0.05).Conclusion Linc00941 is positively correlated with the malignancy of gastric cancer.Silencing Linc00941 can reduce the malignancy of gastric cancer cells by reducing the expression of TGF-β1/SMAD4,providing a new basis for the clinical diagnosis and treatment of gastric cancer.