miR-5047-PTEN/PI3K/AKT/Slug变异环路介导IGF-I促进乳腺癌细胞肿瘤干性的研究

肿瘤干细胞在肿瘤复发转移耐药中发挥重要作用。我们前期研究发现一个新的miR-5047在乳腺癌肿瘤球中表达明显上调。初步研究显示，miR-5047可直接靶向抑癌基因PTEN，活化PI3K/AKT通路和Slug转录因子，并反馈诱导其表达，形成变异环路。此外，miR-5047在乳腺癌中被IGF-I通过Slug诱导参与了IGF-I促进乳腺癌上皮间质转化(EMT)及肿瘤干性过程。我们拟对其机制进行深入研究，验证miR-5047在乳腺癌细胞中通过调控PTEN/PI3K/AKT/Slug信号通路反馈诱导其表达形成的变异环路能被IGF-I调控，促进乳腺癌EMT和肿瘤干性特征。进一步证实miR-5047介导IGF-I促进乳腺癌细胞增殖、转移和肿瘤干性。我们的研究将首次确立miR-5047作为候选癌基因，为乳腺癌治疗提供新的靶点。

Cancer stem cells(CSCs) play an important role in tumor recurrence, metastasis and resistance. Our previous study found that the expression levels of a new miR-5047 in tumor spheres of breast cancer cells were significantly up-regulated. Preliminary studies have shown that miR-5047 can directly target tumor suppressor gene PTEN, further activate PI3K / AKT pathway and Slug transcription factor which feedback to induce miR-5047 expression to form a positive feedback loop. In addition, miR-5047 is induced by insulin-like growth factor-I(IGF-I) in breast cancer and may be involved in IGF-I signaling promoting breast cancer epithelial-mesenchymal transition(EMT) and the formation of cancer stem cells. Further we will study on the mechanism that miR-5047 in breast cancer cells can regulate the expression of PTEN / PI3K / AKT / Slug signaling axis to induce the expression of itself, which can be regulated by IGF-I, promote breast cancer EMT and tumor stemness. Further demonstrated that miR-5047 mediates IGF-I to promote breast cancer cell proliferation, metastasis and tumor stemness. Our study firstly reveals miR-5047 as a candidate oncogene, which will provide a new therapeutic target for breast cancer.