miR-205通过JAK2/STAT3信号通路影响三阴性乳腺癌细胞的体外转移活性  

miR-205 Influences the Metastatic Activity of Triple Negative Breast Cancer Cells through JAK2/STAT3 Signaling Pathway

作　　者：张军[1] 李杰[1] 李杏 李鸽姿 赵崇如 陈嘉丽 彭大伟 张天莹 ZHANG Jun;LI Jie;LI Xing;LI Gezi;ZHAO Chongru;CHEN Jiali;PENG Dawei;ZHANG Tianying(Department of Thyroid and Breast Surgery,Shenzhen Hospital,the Second Xiangya Hospital of Central South University,Shenzhen,Guangdong,518101,China)

机构地区：[1]中南大学湘雅二医院深圳医院(深圳市前海蛇口自贸区医院)甲状腺乳腺外科,广东省深圳市518101

出　　处：《医学分子生物学杂志》2023年第4期310-315,共6页Journal of Medical Molecular Biology

基　　金：深圳市南山区科技计划项目(No.NS2022033)。

摘　　要：目的探究miR-205与JAK2/STAT3在三阴性乳腺癌发展中的作用关系,以期为三阴性乳腺癌的治疗提供新思路。方法使用实时荧光定量PCR法和Western印迹检测癌组织和癌旁组织中miR-205和JAK2的表达水平。用miR-205 mimic、miR NC、pcDNA3.1 JAK2和pcDNA3.1 NC转染MDA-MB-231细胞后,Western印迹实验检测JAK2途径蛋白的表达。划痕实验检测MDA-MB-231细胞的迁移情况,Transwell实验检测细胞的侵袭能力,集落形成实验分析MDA-MB-231细胞的生长能力,流式细胞术分析MDA-MB-231细胞凋亡情况,荧光素酶报告基因实验分析miR-205和JAK2的相互作用情况。结果在三阴性乳腺癌组织中,miR-205表达水平降低,JAK2的表达水平升高。通过在MDA-MB-231细胞实验中过表达miR-205后,三阴性乳腺癌细胞的生长、侵袭和转移能力均受到抑制,同时凋亡率显著增加。另外,在MDA-MB-231细胞实验中过表达JAK2后,三阴性乳腺癌细胞的生长、侵袭和转移能力均增加,同时凋亡率显著降低。荧光素酶报告基因实验发现,miR-205能够靶向抑制JAK2活性。结论miR-205能够靶向调控JAK2/STAT3途径,进而抑制三阴性乳腺癌细胞的生长、侵袭和转移,并同时促进三阴性乳腺癌细胞凋亡。Objective To explore the relationship between miR-205 and JAK2/STAT3 in the development of triple negative breast cancer(TNBC),so as to provide new ideas for the treatment of TNBC.Methods qRT-PCR and Western blotting were used to detect the expression levels of miR-205 and JAK2 in cancer tissues and adjacent tissues.The expression levels of JAK2 pathway related proteins were detected by Western blotting in MDA-MB-231 cell line after cells were transfected with miR-205 mimic,miR NC,pcDNA3.1 JAK2 or pcDNA3.1 NC.The migration of MDA-MB-231 cells was detected by wound healing assay,the invasiveness of cells was detected by transwell test,the growth ability of MDA-MB-231 cells was analyzed by colony formation assay,the apoptosis was analyzed by flow cytometry,and the interaction between miR-205 and JAK2 was verified by dual luciferase gene reporter assay.Results In TNBC tissues,the expression level of miR-205 decreased and the expression level of JAK2 increased.After overexpression of miR-205 in MDA-MB-231 cells,the capacity of growth,invasion and metastasis of cells were suppressed,while the apoptosis rate was significantly increased.On the contrary,after overexpression of JAK2 in the MDAMB-231 cells,the capacity of growth,invasion and metastasis of cells were enhanced,and the apoptosis rate was significantly reduced.The dual luciferase gene reporter assay revealed that miR-205 can target and inhibit JAK2 activity.Conclusion miR-205 can target JAK2/STAT3 pathway,inhibit the growth,invasion and metastasis of TNBC cells,and promote the apoptosis of TNBC cells.

关 键 词：miR-205 JAK2 STAT3 三阴性乳腺癌 转移 

分 类 号：R737.9[医药卫生—肿瘤]