机构地区:[1]成都市中西医结合医院胸外科,610041 [2]成都市中西医结合医院骨科,610041 [3]成都市中西医结合医院检验科,610041
出 处:《临床外科杂志》2023年第6期562-567,共6页Journal of Clinical Surgery
基 金:成都市医学科研课题(编号:2018010)。
摘 要:目的探讨富含亮氨酸的α2糖蛋白1(LRG1)通过Runt相关转录因子1(RUNX1)/骨桥蛋白(OPN)轴对非小细胞肺癌(NSCLC)细胞增殖、迁移和侵袭的调节作用。方法测定体外培养的人Ⅱ型肺泡上皮细胞与人NSCLC细胞系A549、NCI-H838、NCI-H1650中LRG1、RUNX1与OPN表达,以随机数字表法将体外培养的人NSCLC细胞系A549随机分为对照组、LRG1敲低组、阴性对照组、RUNX1过表达组、LRG1敲低+RUNX1过表达组,细胞分组转染质粒后,检测各组A549细胞增殖、凋亡、迁移、侵袭、凋亡蛋白(Bcl-2、caspase-3、Bax)及上皮间质转化标志蛋白(N-cadherin、E-cadherin)表达、LRG1与RUNX1、OPN表达。结果与人Ⅱ型肺泡上皮细胞相比,人NSCLC细胞系A549、NCI-H838、NCI-H1650中LRG1、RUNX1与OPN mRNA与蛋白表达升高(P<0.05)。与对照组相比,LRG1敲低组细胞EdU阳性率、迁移率、侵袭数、细胞LRG1、RUNX1与OPN mRNA及蛋白表达、细胞Bcl-2、N-cadherin蛋白表达降低,差异有统计学意义(P<0.05),凋亡率、细胞caspase-3、Bax、E-cadherin蛋白表达升高,差异有统计学意义(P<0.05);RUNX1过表达组各指标变化与LRG1敲低组相反,且过表达RUNX1可逆转敲低LRG1对细胞各指标的作用。结论敲低LRG1可通过下调RUNX1、OPN表达而抑制NSCLC细胞增殖、迁移和侵袭,并促进其凋亡。Objective To investigate the regulatory effect of leucine-rich-alpha2-glycoprotein 1(LRG1)on the proliferation,migration and invasion of non-small cell lung cancer(NSCLC)cellsvia the Runt-related transcription factor 1(RUNX1)/osteopontin(OPN)axis.Methods To determin the expression of LRG1,RUNX1 and OPN in cultured human type II alveolar epithelial cells and human NSCLC cell lines A549,NCI-H838 and NCI-H1650.The human NSCLC cell line A549 cultured in vitro was randomly divided into control group,LRG1 knockdown group,negative control group,RUNX1 overexpression group,LRG1 knockdown+RUNX1 overexpression group by random number table method,after cells were grouped and transfected with plasmids,to detect the proliferation,apoptosis,migration,invasion,the expression of apoptosis proteins(Bcl-2,caspase-3,Bax)and epithelial-mesenchymal transition marker proteins(N-cadherin,E-cadherin),the expressions of LRG1,RUNX1 and OPN in A549 cells in each group.〖WTHZ〗Results Compared with human type II alveolar epithelial cells,the mRNA and protein expressions of LRG1,RUNX1 and OPN in human NSCLC cell lines A549,NCI-H838 and NCI-H1650 higher(P<0.05).Compared with the control group,the positive rate of EdU,the migration rate,the number of invasion,the mRNA and protein expressions of LRG1,RUNX1 and OPN,and the protein expression of Bcl-2 and N-cadherin in the LRG1 knockdown group were decreased(P<0.05),and the apoptosis rate and the protein expression of caspase-3,Bax,and E-cadherin were increased(P<0.05);The changes of various indicators in RUNX1 overexpression group were contrary to those in LRG1 knockdown group,and the overexpression of RUNX1 could reverse the effects of LRG1 knockdown on various indicators of cells.Conclusion Knockdown of LRG1 can inhibit the proliferation,migration and invasion of NSCLC cells and promote their apoptosis by down-regulating the expressions of RUNX1 and OPN.
关 键 词:富含亮氨酸的α2糖蛋白1 RUNX1/OPN信号 非小细胞肺癌 增殖 迁移侵袭
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