TCF7L2通过PLAUR促进三阴性乳腺癌的增殖和侵袭迁移

TCF7L2 promotes the proliferation,invasion,and migration of TNBC through PLAUR

目的:研究转录因子7样2(TCF7L2)通过纤溶酶原激活受体表面蛋白(PLAUR)对三阴性乳腺癌(TNBC)细胞增殖及侵袭迁移能力的影响及其潜在机制。方法:利用瞬时转染技术在TNBC细胞中沉默PLAUR,观察对TNBC细胞克隆、EdU、MTT、细胞划痕、Transwell小室侵袭迁移实验结果的影响。通过在裸鼠体内进行皮下成瘤实验,检验PLAUR对TNBC细胞增殖能力的影响。在TNBC细胞中沉默TCF7L2的表达,验证TCF7L2通过PLAUR促进细胞增殖和侵袭。结果:与对照组相比,TNBC细胞系MDA-MB-231和MDA-MB-468中的PLAUR沉默明显抑制了细胞的增殖、迁移及侵袭能力(P<0.01)。在裸鼠皮下肿瘤模型中,PLAUR沉默组的肿瘤体积和质量均明显低于对照组(P<0.01)。此外在沉默TCF7L2后,TNBC细胞系中PLAUR的表达水平明显下调,且伴随着迁移及侵袭能力的下调(P<0.01)。结论:TCF7L2可通过PLAUR促进TNBC细胞的增殖和侵袭迁移能力。

Objective:To study the effect of transcription factor 7-like 2(TCF7L2)on the proliferation,invasion,and migration abilities of triple-negative breast cancer(TNBC)cells through plas minogen activator urokinase receptor(PLAUR)and its potential mechanisms.Methods:Transient transfection technique was applied to silence PLAUR in TNBC cells to observe its impact on the results of cell colony formation,EdU,MTT,cell scratch,and Transwell chamber invasion and migration assays.The effect of PLAUR on the proliferative ability of TNBC cells was tested by subcutaneous tumor formation experiments in nude mice.The expression of TCF7L2 was silenced in TNBC cells to verify the promoting effects of TCF7L2 on cell proliferation and invasion through PLAUR.Results:Compared with the control group,silencing PLAUR in TNBC cell lines MDA-MB-231 and MDA-MB-468 significantly inhibited the cell proliferation,migration,and invasion abilities(P<0.01).In the subcutaneous tumor model in nude mice,the tumor volume and weight in the PLAUR silencing group were significantly lower than those in the control group(P<0.01).Furthermore,the expression level of PLAUR,migration and invasion abilities were significantly downregulated in TNBC cell lines after TCF7L2 silencing(P<0.01).Conclusions:TCF7L2 can promote the proliferation,invasion and migration abilities of TNBC cells through PLAUR.