摘要
目的:探讨特异AT富含序列结合蛋白2(SATB2)在乳腺癌中的作用,并分析敲减SATB2对乳腺癌细胞恶性生物学行为的影响和潜在机制。方法:用GEPIA数据库分析SATB2在乳腺癌中的表达,用Kaplan-Meier Plotter数据库分析其对乳腺癌患者总生存期(OS)的影响。免疫组化检测乳腺癌组织中SATB2的蛋白表达。将人乳腺癌细胞株MDA-MB-231与MCF-7分为si-Con组(转染si-Con)和si-SATB2组(转染si-SATB2)。用EdU染色和集落形成实验评估细胞增殖能力,用Transwell方法检测乳腺癌细胞的迁移、侵袭能力及其对内皮细胞的招募能力,用小管形成实验检测其诱导内皮细胞血管生成能力,Western blot检测血管内皮生长因子A(VEGFA)、基质金属蛋白酶2(MMP-2)、MMP-9、激活STAT蛋白抑制因子1(PIAS1)和组蛋白脱乙酰基酶1(HDAC1)的表达。结果:与正常乳腺组织比较,乳腺癌中SATB2的基因和蛋白水平均升高(P<0.05)。与SATB2低表达组比较,SATB2高表达组的乳腺癌患者的OS显著缩短(P<0.05)。与si-Con组比较,si-SATB2组乳腺癌细胞的增殖、迁移和侵袭及招募内皮细胞和诱导血管形成能力均降低(P<0.05);乳腺癌细胞中VEGFA、MMP-2、MMP-9、PIAS1和HDAC1表达均下调(P<0.05)。结论:敲减SATB2能抑制乳腺癌细胞的增殖、迁移、侵袭和肿瘤血管生成,其机制可能与其抑制VEGFA、MMP-2、MMP-9、PIAS1和HDAC1表达有关。
AIM:To investigate the role of special AT-rich sequence-binding protein 2(SATB2)in breast cancer,and analyze the effects and potential mechanisms of SATB2 knockdown on the malignant biological behavior of breast cancer cells.METHODS:The expression of SATB2 in breast cancer was examined utilizing the GEPIA database,and its impact on overall survival(OS)of breast cancer patients was assessed using the Kaplan-Meier Plotter database.Immunohistochemistry was performed to detect SATB2 protein expression in breast cancer tissue.Human breast cancer cell lines MDA-MB-231 and MCF-7 were divided into two groups:si-Con group(transfected with si-Con)and si-SATB2 group(transfected with si-SATB2).Cell proliferation capacity was evaluated by EdU staining and colony formation assay.Migration and invasion abilities,as well as recruitment abilities to endothelial cells were detected by Transwell assay.The ability of breast cancer cells to induce endothelial cell angiogenesis was examined using a tubule formation assay.The expression levels of vascular endothelial growth factor A(VEGFA),matrix metalloproteinase-2(MMP-2),MMP-9,protein inhibitor of activated STAT1(PIAS1)and histone deacetylase 1(HDAC1)were detected by Western blot.RESULTS:Compared with normal breast tissue,the gene and protein levels of SATB2 were found to be increased in breast cancer(P<0.05).Compared with low SATB2 expression group,the OS of breast cancer patients in high SATB2 expression group was significantly shortened(P<0.05).Compared with si-Con group,the proliferation,migration and invasion of breast cancer cells,as well as the ability to recruit endothelial cells and induce angiogenesis were decreased in si-SATB2 group(P<0.05),and the expressions of VEGFA,MMP-2,MMP-9,PIAS1 and HDAC1 in breast cancer cells were down-regulated(P<0.05).CONCLUSION:Knockdown of SATB2 can inhibit the proliferation,migration,invasion of breast cancer cells and tumor angiogenesis,and its mechanism may be related to the inhibition of VEGFA,MMP-2,MMP-9,PIAS1 and HDAC1 expressions.
作者
吴坤琳
严乾壹
王德星
缪秀英
张惠灏
WU Kunlin;YAN Qianyi;WANG Dexing;LIAO Xiuying;ZHANG Huihao(Department of Thyroid and Breast Surgery,the First Affiliated Hospital,Fujian Medical University,Fuzhou 350005,China;Department of General Surgery,Second Division,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University,Fuzhou 350212,China;First Clinical Medical College,Fujian Medical University,Fuzhou 350005,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2023年第11期1994-2002,共9页
Chinese Journal of Pathophysiology
基金
福建省自然科学基金资助项目(No.2020J01944,No.2022J01698)。
