Sp1促进A549细胞增殖、EMT、侵袭和血管生成的研究  

Sp1 Promotes Proliferation,EMT,Invasion and Angiogenesis in A549 Cells

作　　者：秦书华 彭俊[2] 高创创 桂浩鑫 邵钰婷 郝倩[1] 向诚[1] 徐天瑞[1] 刘莹 QIN Shuhua;PENG Jun;GAO Chuangchuang;GUI Haoxin;SHAO Yuting;HAO Qian;XIANG Cheng;XU Tianrui;LIU Ying(Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming 650500,China;Thoracic Surgery,Yunnan First People's Hospital,Kunming 650034,China;Institute of Life Sciences,Jinzhou Medical University,Jinzhou,Liaoning 121001,China)

机构地区：[1]昆明理工大学生命科学与技术学院,云南昆明650500 [2]云南省第一人民医院胸外科,云南昆明650034 [3]锦州医科大学生命科学研究院,辽宁锦州121001

出　　处：《昆明理工大学学报（自然科学版）》2022年第3期123-130,共8页Journal of Kunming University of Science and Technology(Natural Science)

基　　金：国家自然科学基金项目(81560455)。

摘　　要：研究Sp1转录调控原癌基因c-Met促进肺癌A549细胞增殖、EMT转化、侵袭和血管生成,抑制A549细胞凋亡的分子机制.首先采用双荧光素酶报告基因和染色质免疫共沉淀(ChIP)法检测Sp1与c-Met基因启动子结合情况.之后,在A549细胞中过表达和沉默表达Sp1,Western-blotting法和免疫荧光法研究Sp1转录调控c-Met,促进A549细胞增殖、EMT转化、血管生成,侵袭并抑制A549细胞凋亡的分子机制.与癌旁组织和正常组织相比,在肺癌组织样本中,Sp1和c-Met均呈现高表达;Sp1能够与c-Met基因启动子结合;Sp1转录调控c-Met通过激活c-Met-ERK通路,促进A549细胞增殖、抑制A549细胞凋亡;Sp1转录调控c-Met亦能促进A549细胞EMT转化,侵袭和血管生成.Sp1转录调控c-Met能够促进A549细胞增殖、EMT转化,侵袭和血管形成,抑制A549细胞凋亡.在肺癌发生发展进程中,Sp1转录调控c-Met发挥重要作用.This article aims to investigate the molecular mechanism by which Sp1 transcriptionally regulates the proto-oncogene c-Met to promote proliferation,EMT transformation,invasion,migration and angiogenesis of lung cancer A549 cells and inhibit apoptosis of A549 cells.The binding of Sp1 to the c-Met gene promoter was first detected by using a dual luciferase reporter gene and chromatin immunoprecipitation(ChIP)method.Subsequently,Sp1 was overexpressed and silently expressed in A549 cells,and the molecular mechanisms by which Sp1 transcriptionally regulates c-Met to promote A549 cell proliferation,EMT transformation,angiogenesis,invasion,migration,and inhibit A549 cell apoptosis were investigated by Western-blotting and immunofluorescence assays.Both Sp1 and c-Met were highly expressed in lung cancer samples compared to paraneoplastic and normal tissues.Sp1 is able to bind to the c-Met gene promoter.Sp1 transcriptional regulation of c-Met promotes A549 cell proliferation and inhibits A549 cell apoptosis through activation of the c-Met-ERK pathway.Sp1 transcriptional regulation of c-Met also promotes EMT transformation,invasion,migration and angiogenesis in A549 cells.Sp1 transcriptional regulation of c-Met promotes A549 cell proliferation,EMT transformation,invasion,migration and angiogenesis,and inhibits A549 cell apoptosis.Sp1 transcriptional regulation of c-Met plays an important role in the development of lung cancer.

关 键 词：Sp1转录因子 细胞增殖 原癌基因C-MET EMT转化 侵袭 血管生成 

分 类 号：R734.2[医药卫生—肿瘤]