miR-484通过SORBS2/MEK-ERK通路调控乳腺癌细胞增殖、转移和自噬  

miR-484 Regulates the Proliferation,Metastasis and Autophagy of Breast Cancer Cells Through SORBS2/MEK-ERK Pathway

作　　者：潘鑫 刘析璘 郭敏 PAN Xin;LIU Xilin;GUO Min(Medical College of Jinzhou Medical University,Jinzhou 121000,Liaoning,China;Hebei Oriental University,Langfang 065000,Hebei,China)

机构地区：[1]锦州医科大学医疗学院,中国辽宁锦州121000 [2]河北东方学院,中国河北廊坊065000

出　　处：《生命科学研究》2024年第2期103-112,127,共11页Life Science Research

基　　金：2023年国家级大学生创新训练计划项目(202313213005)。

摘　　要：为了分析miR-484在乳腺癌组织和细胞中的表达情况,研究miR-484在乳腺癌细胞增殖、转移和自噬过程中的作用机制,首先,采用GEO数据库分析乳腺癌组织中差异表达miRNA谱,并用实时荧光定量PCR在临床乳腺癌组织及其配对的癌旁组织中检测miR-484的表达情况;其次,利用miR-484模拟物、抑制剂检测miR-484对MCF-7乳腺癌细胞增殖、转移和自噬能力的影响;再次,预测miR-484的调控基因并进行验证,同时构建Sorbin和SH3结构域包含蛋白2(Sorbin and SH3 domain-containing protein 2,SORBS2)过表达载体,检测SORBS2对乳腺癌细胞增殖、转移和自噬能力的影响;最后,用Western-blot分析miR-484调控下MCF-7细胞中丝裂原活化的胞外信号调节激酶(mitogen-activated extracellular signal-regulated kinase,MEK)/p-MEK和胞外信号调节激酶(extracellular signal-regulated kinase,ERK)/p-ERK的蛋白质含量变化。结果显示,miR-484在乳腺癌组织及细胞中高表达,具有提高乳腺癌细胞增殖、迁移和侵袭能力以及降低乳腺癌细胞自噬能力的作用;而且,miR-484可通过下调SORBS2并激活MEK/ERK通路参与乳腺癌的发生发展。In order to analyze the expression of miR-484 in breast cancer tissues and cells,and its mechanism in breast cancer cell proliferation,metastasis and autophagy,the differentially expressed microRNAs(miRNAs)in breast cancer tissues were analyzed using GEO database,and the expression of miR-484 was detected by real-time fluorescence quantitative PCR in clinical breast cancer tissues and their paired paracancerous tissues.The effects of miR-484 on the proliferation,metastasis and autophagy of MCF-7 breast cancer cells were detected by the miR-484 mimic and inhibitor.Then,the target gene of miR-484 was predicted and verified,the Sorbin and SH3 domain-containing protein 2(SORBS2)overexpression vector was constructed to detect the effects of SORBS2 on the proliferation,metastasis and autophagy of MCF-7 cells.Finally,the protein contents of mitogen-activated extracellular signal-regulated kinase(MEK)/p-MEK and extracellular signal-regulated kinase(ERK)/p-ERK in MCF-7 cells under the regulation of miR-484 were analyzed by Western-blot.The results showed that miR-484 was highly expressed in breast cancer tissues and cells,and improved the proliferation,migration,invasion of breast cancer cells and reduced their autophagy ability.Meanwhile,miR-484 could down-regulate SORBS2 and activate MEK/ERK pathway to participate in the occurrence and development of breast cancer.

关 键 词：乳腺癌 miR-484 Sorbin和SH3结构域包含蛋白2(SORBS2) 转移 自噬 

分 类 号：Q25[生物学—细胞生物学] R737.9[医药卫生—肿瘤]