miR-4429靶向PIK3R1调控细胞内质网应激通路影响乳腺癌恶性表型的机制  

The mechanism of miR-4429 regulate endoplasmic reticulum stress pathway through PIK3R1 to affect the malignant phenotype of breast cancer

作　　者：张英辉[1] 沈恋迪 李锐 尚晓慧 曹玲聪 严俊 ZHANG Yinghui;SHEN Liandi;LI Rui;SHANG Xiaohui;CAO Lingcong;YAN Jun(Department of Breast,Jiading District Maternal and Child Health Hospital,Shanghai 201822,China;Department of Oncology,Jiading District Central Hospital,Shanghai 201800,China)

机构地区：[1]上海市嘉定区妇幼保健院乳腺科,上海201822 [2]上海市嘉定区中心医院肿瘤内科,上海201800

出　　处：《现代肿瘤医学》2024年第16期2951-2958,共8页Journal of Modern Oncology

基　　金：上海市嘉定区科委课题(编号:JDKW-2022-0041)。

摘　　要：目的:探究微小RNA(miRNA)miR-4429对乳腺癌细胞MDA-MB-231增殖、侵袭和凋亡的影响;并探究其与内质网应激相关通路基因PIK3R1的靶向关系及对内质网应激相关通路的调控作用。方法:通过脂质体转染法构建miR-4429过表达及敲低的MDA-MB-231细胞模型,并通过实时荧光定量PCR(qRT-PCR)检测其效率;MTT法、克隆形成实验、Annexin-PI染色实验和Transwell实验分别检测MDA-MB-231细胞的增殖、凋亡和侵袭;双荧光素酶报告基因实验和Western blot验证miR-4429和PIK3R1靶向关系,qRT-PCR和Western blot探究miR-4429对内质网应激通路的调控。结果:成功建立miR-4429过表达及敲低的MDA-MB-231细胞模型;miR-4429 mimic组中MDA-MB-231细胞的增殖、侵袭能力均低于其Ctrl组,凋亡能力高于其Ctrl组(均P<0.05);miR-4429能够靶向性结合PIK3R1并抑制PIK3R1的蛋白表达,同时下调内质网应激通路相关基因。结论:miR-4429靶向性结合PIK3R1并下调内质网应激通路相关基因,抑制乳腺癌细胞的增殖和侵袭,促进凋亡,提示miR-4429可能是乳腺癌治疗的潜在靶点。Objective:To investigate the effect of microRNA(miRNA)miR-4429 in breast cancer cells MDA-MB-231 proliferation,migration and apoptosis,and its regulation effect on PIK3R1 and endoplasmic reticulum(ER)stress pathway.Methods:Construct miR-4429 overexpression and knockdown MDA-MB-231 cell model by liposome transfection,and detect its efficiency through qRT-PCR.MTT assay,clone formation assay,Annexin-PI staining assay and Transwell assay were used to detect the proliferation,apoptosis,and invasion of MDA-MB-231 cells,respectively.Dual-luciferase experiment and Western blot were used to verify the targeting relationship between miR-4429 and PIK3R1.qRT-PCR and Western blot were used to investigate the regulation of miR-4429 on the ER stress pathway.Results:Established miR-4429 overexpression and knockdown MDA-MB-231 cell model.The proliferation and invasion ability of MDA-MB-231 cells in the miR-4429 mimic group were lower than those in its Ctrl group,while the apoptosis ability was higher than that in its Ctrl group(P<0.05).miR-4429 could target to PIK3R1 and suppress its protein expression,and downregulate genes related to the ER stress pathway.Conclusion:miR-4429 targets to PIK3R1 and downregulates ER stress pathway related genes expression,inhibits the proliferation and invasion of breast cancer cells and promotes apoptosis,suggesting that miR-4429 may be a potential target for the treatment of breast cancer.

关 键 词：乳腺癌 miR-4429 内质网应激 PIK3R1 

分 类 号：R737.9[医药卫生—肿瘤]