Let-7通过抑制Wnt信号通路激活而促进食管癌干细胞不对称分裂的研究

许峰1 ，程巧莲1，张忆雯2 , 3 ，杜宁2 ，崔晓海2 ，张佳2 ，孙欣2 ，任宏2

（1.山西省临猗县第二人民医院，山西 运城，044102；2.西安交通大学第一附属医院肿瘤中心，胸外二科， 陕西 西安，710061；3.西安交通大学第二附属医院胸心外科，陕西 西安，710004）

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摘要：

目的 研究Let-7对食管癌干细胞分离模式的影响。方法 检测Let-7对食管癌ECA-109及ECA-9706细胞系中干细胞亚群的耐药性及自我更新能力维持的机制。结果 Let-7抑制食管癌干细胞的对称分裂，抑制了干细胞的微球体形成，Wnt通路激活剂及荧光素酶报告基因实验验证了Let-7对Wnt通路的直接调控，Let-7通过抑制食管癌干细胞对称分裂的比例, 促进不对称分裂的发生，降低了干细胞亚群的自我更新能力，改善化疗耐药。结论 Let-7通过抑制食管癌干细胞对称分裂的比 例，降低了干细胞对氟尿嘧啶及多西他赛的耐药性，可改善食管癌患者预后。

关键词：食管癌；食管癌干细胞；Wnt 信号通路；Let-7；分裂模式

中图分类号：R737.9文献标志码：A文章编号：2096-1413(2017)16-0008-05

Let-7 stimulates asymmetric division of esophageal cancer stem-like cells via a Wnt pathway repression manner
XU Feng 1, CHENG Qiao-lian 1, ZHANG Yi-wen 2,3, DU Ning 2, CUI Xiao-hai 2, ZHANG Jia 2, SUN Xin 2, REN Hong 2


(1. the Second Hospital of Linyi County, Yuncheng 044102; 2. Cancer Center, the Second Department
of Thoracic Surgery, the First Affiliated Hospital of Xi`an Jiaotong University, Xi`an 710061; 3. Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Xi`an Jiaotong University, Xi`an 710004, China)

ABSTRACT: Objective To explore the Let-7 functions in regulations of esophageal cancer stem cells seperation mode. Methods Retrospectively detected Let-7 for therapy resistant and cells` renewal mechanisms in ECA-109 and ECA-9706 esophageal cancer stem cells subgroup. Results Wnt activation was respond for symmetric division and the formation of the stem cell microsphere, which could be blocked by Let-7 overexpression. Let-7 was verified to regulate of Wnt pathways by the experiments of Wnt pathways activator and luciferase report gene. Let-7 promotes asymmetric division of esophageal cancer stem cells, which resulted in stem cells` renewal repression. Wnt activation of self-renewal could be blocked by Let -7 overexpression, and Let -7 sensitization of adjuvant therapy was achieved through Wnt signaling inhibition. Conclusion Based on the novel roles of stem cells ratio and crucial suppressive functions of Let -7, the detection and targeted therapy of cancer stem cells will pave the way for improving prognosis and the response of comprehensive treatment.
KEYWORDS: esophageal cancer; cancer stem cells; Wnt signaling; Let-7; division mode

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