LncRNA H19介导的let-7表达下调对食管癌细胞上皮间质转化的影响

LncRNA H19 promotes epithelial-mesenchymal transition via downregulation of let-7 in esophageal squamous cell carcinoma

目的探讨长非编码RNA(Long noncoding RNA,LncRNA)H19介导食管癌细胞上皮间质转化(Epithelial-Mesenchymal Transition,EMT)的作用及机制。方法收集食管癌临床组织样本48例,通过qRT-PCR检测癌组织及癌旁组织中H19和let-7的表达,同时统计分析H19与食管癌患者临床病理参数及术后生存时间的相关性。通过慢病毒转染敲低H19在食管癌细胞中的表达水平,分别运用Western blot和qRT-PCR,检测EMT相关蛋白及微小RNA(microRNA,miRNA)let-7的表达。结果qRT-PCR检测发现食管癌组织中H19表达水平显著上调,且与肿瘤浸润深度及预后不良相关(P<0.05)。Western blot检测发现敲低H19表达后,食管癌细胞中E-cadherin表达上调,β-catenin、Vimentin和Slug表达均下调,与空白对照组和阴性对照组比较差异均有统计学意义(P<0.05)。H19在食管癌组织中高表达的同时,let-7表达下调(P<0.05),在细胞水平敲低H19的表达后,let-7表达增多,与空白对照组和阴性对照组比较差异均有统计学意义(P<0.05)。结论H19可能通过负调控let-7的表达,从而介导食管癌EMT过程。

Objective To investigate the role and mechanism of long noncoding RNA(lncRNA)H19 in epithelial mesenchymal transition(EMT)of esophageal squamous cell carcinoma(ESCC).Methods The expression of H19 and let-7 in 48 cases of ESCC were detected by qRT PCR,and the correlation between H19 and clinicopathological parameters and prognosis were analyzed.Western blot and qRT PCR were used to detect the expression of EMT related protein and microRNA(miRNA)let-7.Results The expression of H19 was up-regulated in ESCC,which was correlated with tumor invasion depth and poor prognosis(P<0.05).The expression of E-cadherin was up-regulated and the expression ofβ-Catenin,Vimentin and Slug were down regulated in ESCC cells after knockdown of H19 expression,and the differences were statistically significant compared with blank control group and negative control group(P<0.05).Furthermore,the expression of let-7 was down regulated while the expression of H19 was high in vivo(P<0.05).After the expression of H19 was knocked down,the expression of let-7 was increased,and the difference was statistically significant compared with the blank control group and negative control group(P<0.05).Conclusion H19 may be responsible for the EMT process of ESCC by negative regulation of let-7 expression.