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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展和转移。

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.

机构信息

Department of Breast and Neck Surgery, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5301-5314. doi: 10.26355/eurrev_201906_18197.

Abstract

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.

摘要

目的

三阴性乳腺癌通常具有恶性程度高、易复发转移、预后差等特点,但目前尚未找到有效的三阴性乳腺癌治疗方法。本研究探讨了外泌体运输 Let-7a 并调控 c-Myc 基因的作用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的思路。

患者与方法

基于 c-Myc 和 Let-7a 在三阴性乳腺癌发生发展中的作用的既往研究,分别构建了 c-Myc 敲除和 Let-7a 过表达的三阴性乳腺癌细胞系,以评估 c-Myc、Let-7a 以及外泌体传递 Let-7a 对三阴性乳腺癌发生发展的影响。

结果

外泌体介导的 Let-7a 通过与 c-Myc 基因 3'UTR 区域结合并沉默 c-Myc 表达,抑制 MDA-MB-231 细胞的增殖、迁移和侵袭。

结论

本研究揭示了 c-Myc、Let-7a 和外泌体在三阴性乳腺癌发生发展中的作用,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。

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