MiR-205 inhibits the invasion and migration of esophageal squamous cell carcinoma by modulating SMAD1 expression  

作　　者：Baoyu Liang Yan Wu Xu Han Xiaofei Zheng Qimin Zhan Tong Tong 

机构地区：[1]State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College [2]Beijing Institute of Radiation Medicine, Military Medical Sciences

出　　处：《Chinese Science Bulletin》2014年第19期2232-2239,共8页

基　　金：supported by the National Basic Research Program(2009CB521801 and 2010CB912801)

摘　　要：Esophageal squamous cell carcinoma(ESCC)is one of the most lethal cancers worldwide.In this study,we aimed to investigate the underlying mechanisms of metastasis inhibition by miR-205 in ESCC.In microRNA(miRNA)array and quantitative RT-PCR analyses,we found that the expression level of miR-205 was significantly lower in patients with lymph node metastasis compared with that in patients without lymph node metastasis.After transfection of miR-205 mimics or inhibitors into ESCC cell lines,a significant negative correlation was observed between the expression level of miR-205 and Smad1.In luciferase reporter assays,we revealed that miR-205 inhibited the expression of SMAD1 by targeting the 30untranslated region(30-UTR)of SMAD1 mRNA in ESCC cells.Furthermore,our results showed that miR-205 suppressed the invasion and migration of ESCC cells,whereas Smad1 increased their invasion and migration.Taken together,our study demonstrates that miR-205 functions as a suppressor of tumor metastasis by regulating SMAD1expression through targeting the 30-UTR of SMAD1 mRNAin ESCC.Therefore,miR-205 may be a potential therapeutic target for miRNA-based therapy of ESCC.Esophageal squamous cell carcinoma （ESCC） is one of the most lethal cancers worldwide. In this study, we aimed to investigate the underlying mechanisms of metastasis inhibition by miR-205 in ESCC. In microRNA （miRNA） array and quantitative RT-PCR analyses, we found that the expression level of miR-205 was significantly lower in patients with lymph node metastasis compared with that in patients without lymph node metastasis. After transfection of miR-205 mimics or inhibitors into ESCC cell lines, a significant negative correlation was observed between the expression level of miR-205 and Smad 1. In luciferase reporter assays, we revealed that miR- 205 inhibited the expression of SMAD1 by targeting the 3＇ untranslated region （3＇-UTR） of SMAD1 mRNA in ESCC cells. Furthermore, our results showed that miR-205 sup- pressed the invasion and migration of ESCC cells, whereas Smadl increased their invasion and migration. Taken together, our study demonstrates that miR-205 functions as a suppressor of tumor metastasis by regulating SMAD1 expression through targeting the 3＇-UTR of SMAD1 mRNAin ESCC. Therefore, miR-205 may be a potential therapeutic target for miRNA-based therapy of ESCC.

关 键 词：食管癌细胞 鳞状细胞癌 RT-PCR分析 miRNA 入侵 SMAD蛋白 微小RNA 基因分析 

分 类 号：R735.1[医药卫生—肿瘤]