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

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。

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

ObjectiveTo investigate the effect and mechanism of miR-223 in regulating breast cancer cells and osteoclast in bone metastasis microenvironment. MethodsThe 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. ResultsThe 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. ConclusionmiR-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.