Inhibition effect of exosomes-mediated Let-7a on the development and metastasis of triple negative breast cancer by down-regulating the expression of c-Myc

Inhibition effect of exosomes-mediated Let-7a on the development and metastasis of triple negative breast cancer by down-regulating the expression of c-Myc
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外泌体介导的Let-7a通过下调c-Myc表达抑制三阴性乳腺癌的发生和转移

DOI:
10.26355/eurrev_201906_18197
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发表时间:
2019-06-01
影响因子:
3.3
通讯作者:
Ma, B-L
Ma, B-L
中科院分区:
医学4区
文献类型:
--
作者:
Du, J.;Fan, J. J.;Ma, B-L

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目的:三阴性乳腺癌具有恶性程度高、易复发和转移的特点。且预后不良。然而,三阴性乳腺癌的有效治疗方法尚未确定。我们的研究探讨了外泌体转运Let-7a和调节c-Myc基因的潜在机制及其在三阴性乳腺癌发生发展中的作用,为三阴性乳腺癌的靶向治疗提供新思路。 患者和方法:在既往研究c-Myc和Let-7a在三阴性乳腺癌发生发展中作用的基础上,通过c-Myc构建了三阴性乳腺癌细胞系 Let-7a 的敲除和过度表达。分别。评估 c-Myc 的效果。和 Let-7a,以及传递 Let-7a 的外泌体对三阴性乳腺癌发展的影响。结果:由外泌体介导的 Let-7a 通过与 c-Myc 基因的 3'UTR 区域结合并沉默 c-Myc 表达来抑制 MDA-MB-231 细胞的增殖、迁移和侵袭。结论:我们的研究揭示了 c-Myc、Let-7a 和外泌体在三阴性乳腺癌发展中的作用。为进一步利用外泌体构建肿瘤杀伤载体以及探索三阴性乳腺癌的特异性靶点奠定了理论基础。
OBJECTIVE: Triple negative breast cancer is typically characterized by high malignancy, easy recurrence and metastasis. and poor prognosis. However, effective treatment for triple negative breast cancer has not yet been identified. Our research explores the underlying mechanisms of exosomes in transporting Let-7a and regulating c-Myc gene and their roles in the development of triple negative breast cancer, and to provide new ideas for targeted therapy of triple negative breast cancer.PATIENTS AND METHODS: Based on previous studies that focused on the roles of c-Myc and Let-7a in the development of triple negative breast cancer, triple negative breast cancer cell lines have been constructed by c-Myc knockout and overexpression of Let-7a. respectively. to evaluate the effects of c-Myc. and Let-7a, as well as exosomes transmitting Let-7a on the development of triple negative breast cancer.RESULTS: Let-7a, which is mediated by exosomes, inhibited proliferation, migration, and invasion of MDA-MB-231 cells by binding on the 3'UTR region of the c-Myc gene and silencing of the c-Myc expression.CONCLUSIONS: Our study revealed the role of c-Myc, Let-7a, and exosomes in the development of triple negative breast cancer. which lay the theoretical foundation for further usage of exosomes to construct tumor killing vectors and for exploring specific targets for triple negative breast cancer.