


标题: | miR-223通过IGF-1R及NFIA调控乳腺癌细胞及破骨细胞功能的研究 |
摘要: |
目的:探索miR-223在乳腺癌骨转移微环境中调控乳腺癌细胞、破骨细胞的功能及其机制。方法:采用micro-CT检测野生型及miR-223基因敲除小鼠股骨骨小梁骨体积分数、骨密度等相关数据,并对股骨组织病理切片染色,观察miR-223缺失对破骨活动影响。利用RANKL诱导RAW 264.7细胞分化为破骨细胞的体外模型,研究miR-223在其中的作用及机制。通过MDA-MB-231细胞实验研究miR-223对乳腺癌细胞增殖、凋亡功能的调控作用及机制。结果:miR-223基因敲除小鼠股骨破骨活动明显活跃;miR-223过表达可以通过NFIA基因抑制RNAKL诱导的破骨细胞分化成熟,还可通过抑制IGF-1R及PI3K/Akt信号通路,抑制乳腺癌细胞增殖并促进其凋亡。结论:miR-223是骨转移微环境中抑制乳腺癌骨转移发生发展的保护性因子,可通过抑制破骨细胞分化成熟、破骨活动、乳腺癌细胞增殖及促进乳腺癌细胞凋亡来调节乳腺癌骨转移微环境。 |
英文摘要: | Objective:To investigate the effect and mechanism of miR-223 in regulating breast cancer cells and osteoclast in bone metastasis microenvironment. Methods:The role of miR-223 in regulating bone resorption was evaluated by micro-CT and histologic section in miR-223 knockout and C57BL/6 mice. The effect and mechanism of miR-223 in RANKL induced osteoclast formation was investigated. The role and mechanism of miR-223 in regulating breast cancer cell proliferation and apoptosis were investigated in MDA-MB-231 cell line. Results:The osteoclastic resorption was more severe inmiR-223 knockout mice. In vitro, miR-223 could suppress RANKL activating osteocalst formation by targeting NFIA protein. Besides, overexpression of miR-223 inhibited MDA-MB-231 cell proliferation and promoted its apoptosis by targeting IGF-1R and PI3K/Akt pathway. Conclusion:miR-223 is a protective factor in bone metastasis microenvironment, which can suppress bone resorption by inhibiting osteoclast formation, and suppress breast cancer cell proliferation, enhance breast cancer cell apoptosis. |
作者: |
单臻1;李雯2;范远键1;林泽飞2;林颖1;王深明1 |
作者单位: | 广州,中山大学附属第一医院甲状腺乳腺外科1,普通外科实验室2 |
期刊: | 中华普通外科学文献(电子版) |
年.卷(期):页码 | 2020 .14(6):406-410 |
中图分类号: | |
文章编号: | |
引用格式: | [1]单臻1;李雯2;范远键1;林泽飞2;林颖1;王深明1.miR-223通过IGF-1R及NFIA调控乳腺癌细胞及破骨细胞功能的研究[J/CD].中华普通外科学文献(电子版),2020,14(6):406-410 . |
关键词: | 乳腺肿瘤;微RNAs;骨转移;破骨细胞 |
英文关键词: | Breast neoplasms; MicroRNAs; Bone metastasi; Osteoclasts |
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