miR-133b通过靶向调控EGFR影响食管鳞癌的侵袭、转移  

miR-133b regulates esophageal squamous cell carcinoma invasion and metastasis by targeting EGFR

作　　者：曾薇[1] 朱金峰[2] 孔德华[1] 单莉[1] Zeng Wei;Zhu Jinfeng;Kong Dehua(First Dept of Lung Cancer Chemotherapy;Dept of Gastrointestinal Surgery,The Affiliated Cancer Hospital of Xinjiang Medical University,Urumqi 830011)

机构地区：[1]新疆医科大学附属肿瘤医院肺内科一病区,乌鲁木齐830011 [2]新疆医科大学附属肿瘤医院胃肠外科,乌鲁木齐830011

出　　处：《安徽医科大学学报》2018年第7期1010-1016,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金地区基金项目(编号:81660397)

摘　　要：目的探讨miR-133b在食管鳞癌侵袭、转移过程中的作用及机制。方法使用生物信息学工具预测miR-133b的靶基因;双荧光素酶报告基因实验验证miR-133b对靶基因表皮生长因子受体(EGFR)的直接靶向调控作用;细胞增殖实验、划痕实验和Transwell实验检测miR-133b的不同表达对食管鳞癌细胞增殖、迁移和侵袭能力的影响;qRT-PCR验证miR-133b与EGFR在食管鳞癌组织中的表达,并分析miR-133b与食管鳞癌临床病理特征之间的关系。结果生物信息学工具预测EGFR为miR-133b的靶基因,双荧光素酶报告基因实验证实miR-133b可与EGFR 3'UTR片段结合;体外实验通过上调食管鳞癌细胞中miR-133b的表达使细胞的增殖受阻(ECA109:P<0.05,KYSE150:P<0.01);细胞的迁移(ECA109:P<0.01,KYSE150:P<0.01)和侵袭能力(EC5A109:P<0.01,KYSE150:P<0.01)显著减弱。在食管鳞癌组织中miR-133b与EGFR的表达呈负相关性(P<0.01),且miR-133b的表达与食管鳞癌的TNM分期、淋巴结转移显著相关(P均<0.05)。结论 miR-133b可能通过下调EGFR的表达,抑制食管鳞癌的增殖、侵袭和转移,在食管鳞癌的演进中起负调控作用。Objective To investigate the role and mechanism of miR-133 b in cell invasion and metastasis of esophageal squamous cell carcinoma（ESCC）.Methods Bioinformatics tools were used to predict the potential target gene of miR-133 b;dual luciferase reporter gene assay was conducted to verify the prediction.Cell proliferation,wound healing and transwell assay were performed to investigate the effects of miR-133 b on cell proliferation,migration and invasion in esophageal squamous cell carcinoma.qRT-PCR was conducted in a cohort of 33 pairs of ESCC tissues and correspondingly adjacent tissues,then the relationship between the miR-133 b and clinical pathological features weer analysed.Results Bioinformatics tools predicted that EGFR was the potential target gene of miR-133 b,dual luciferase reporter gene assay verified that miR-133 b could bind to a specific sequence of the 3＇-UTR of the mRNA of EGFR.Overexpression of miR-133 b in ESCC cell could inhibit proliferation（ECA109：P0.05,KYSE150：P0.01）,migration（ECA109：P0.01,KYSE150：P0.01） and invasion（ECA109：P0.01,KYSE150：P0.01） in vitro.The results demonstrated that EGFR,the target of miR-133 b in ESCC,which upregulated in ESCC tissues was negatively related to miR-133 b（P0.01）,and miR-133 b was frequently downregulated in esophageal squamous cell carcinoma tissues and its decrement correlated with TNM stage of ESCC and lymphatic metastasis（P both0.05）.Conclusion MiR-133 b may inhibit esophageal carcinoma proliferation,invasion and metastasis by targeting EGFR,it plays a negative role in the progression of ESCC.

关 键 词：食管鳞癌 miR-133b EGFR 侵袭 转移 

分 类 号：R735.1[医药卫生—肿瘤]