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中华普通外科学文献(电子版) ›› 2020, Vol. 14 ›› Issue (06) : 406 -410. doi: 10.3877/cma.j.issn.1674-0793.2020.06.002

所属专题: 总编推荐 文献

论著

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
单臻1, 李雯2, 范远键1, 林泽飞2, 林颖1, 王深明1,()   
  1. 1. 510080 广州,中山大学附属第一医院甲状腺乳腺外科
    2. 510080 广州,中山大学附属第一医院普通外科实验室
  • 收稿日期:2020-09-10 出版日期:2020-12-01
  • 通信作者: 王深明
  • 基金资助:
    广州市珠江科技新星专项资助项目(201806010006)

Investigation of miR-223 in regulating breast cancer cells and osteoclast function via IGF-1R and NFIA

Zhen Shan1, Wen Li2, Yuanjian Fan1, Zefei Lin2, Ying Lin1, Shenming Wang1,()   

  1. 1. Department of Thyroid and Breast Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
    2. Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
  • Received:2020-09-10 Published:2020-12-01
  • Corresponding author: Shenming Wang
  • About author:
    Corresponding author: Wang Shenming, Email:
引用本文:

单臻, 李雯, 范远键, 林泽飞, 林颖, 王深明. 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/OL]. 中华普通外科学文献(电子版), 2020, 14(06): 406-410.

Zhen Shan, Wen Li, Yuanjian Fan, Zefei Lin, Ying Lin, Shenming Wang. Investigation of miR-223 in regulating breast cancer cells and osteoclast function via IGF-1R and NFIA[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2020, 14(06): 406-410.

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。

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.

图1 miR-223基因敲除(-/-)小鼠股骨骨小梁骨量明显减少,而破骨活动明显增强 A为miR-223 -/-小鼠骨小梁骨体积分数(BV/TV)明显低于野生型C57BL/6小鼠(0.07±0.01 vs 0.12±0.01,*P<0.001);B为miR-223 -/-小鼠骨小梁骨密度明显低于野生型小鼠[(156.12±11.60)mg HA/ccmvs(207.46±2.05)mg HA/ccm,*P<0.001];C为实验小鼠股骨切片苏木精-伊红染色结果(×20)
表1 实验小鼠股骨micro-CT扫描数据
图2 上调miR-223可以明显抑制RAW 264.7细胞系中NFIA蛋白的表达 * P<0.05
图3 过表达miR-223可以明显抑制RANKL诱导的破骨细胞分化成熟 A为倒置显微镜下观察TRAP染色阳性多核细胞(×20);B为每个视野下TRAP染色阳性多核细胞平均数量。*P<0.05
图4 Edu检测显示上调miR-223可以明显抑制乳腺癌细胞系MDA-MB-231增殖* P<0.05
图5 Annexin V检测显示miR-223可以明显促进MDA-MB-231细胞凋亡 A、B、C为Annexin V凋亡检测结果;D为凋亡细胞相对比例。* P<0.05
图7 miR-223基因敲除小鼠组织中p-Akt蛋白表达明显高于野生型小鼠* P<0.05
图6 miR-223过表达可以明显抑制IGF-1R、Bcl-2蛋白的表达,抑制Akt磷酸化 A为抑制IGF-1R的表达;B为抑制p-Akt蛋白表达;C为抑制Bcl-2蛋白表达。*P<0.05
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