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微小 RNA-182 靶向 FOXF2 促进三阴性乳腺癌的发展。

MicroRNA-182 targets FOXF2 to promote the development of triple-negative breast cancer.

出版信息

Neoplasma. 2017;64(2):209-215. doi: 10.4149/neo_2017_206.

Abstract

To explore the function of microRNA-182 (miR-182) on MCF7 and MDA-MB-231 cells behaviors, and possible mechanisms of triple-negative breast cancer (TNBC) development. Totally, 30 TNBC patients were enrolled to investigate the correlation between miR-182 expression and TNBC clinical indicators. miR-182 expression in TNBC tissues was measured by qRT-PCR, followed by bioinformatics methods and luciferase reporter assay to investigate whether FOXF2 was a direct target of miR-182. Besides, miR-182 mimics were transfected into MCF7 cells while miR-182 inhibitor into MDA-MB-231 cells, followed by cell proliferation and migration detection. miR-182 expression was significantly correlated with TNBC clinical indicators, such as lymph node metastasis TNM (stage III), intravascular cancer emboli and TNBC recurrence and metastasis. miR-182 expression was significantly higher in TNBC tissues than that in matched normal tissues, and was significantly higher in MDA-MB-231 cells than that in MCF7 cells. miR-182 knockdown inhibited the proliferation and migration of MDA-MB-231 cells while miR-182 overexpression markedly promoted the proliferation and migration of MCF7 cells. Besides, FOXF2 was identified as a direct target of miR-182. Our findings indicate that miR-182 may promote cell proliferation and migration in TNBC possible via down-regulation of FOXF2. miR-182 may serve as a potential target in TNBC treatment.

摘要

为了探索 microRNA-182(miR-182)对 MCF7 和 MDA-MB-231 细胞行为的作用,以及三阴性乳腺癌(TNBC)发展的可能机制。共纳入 30 例 TNBC 患者,以探讨 miR-182 表达与 TNBC 临床指标的相关性。采用 qRT-PCR 检测 TNBC 组织中 miR-182 的表达,然后采用生物信息学方法和荧光素酶报告基因检测,探讨 FOXF2 是否是 miR-182 的直接靶标。此外,将 miR-182 模拟物转染到 MCF7 细胞中,而将 miR-182 抑制剂转染到 MDA-MB-231 细胞中,然后进行细胞增殖和迁移检测。miR-182 的表达与 TNBC 的临床指标显著相关,如淋巴结转移 TNM(III 期)、血管内癌栓以及 TNBC 的复发和转移。miR-182 在 TNBC 组织中的表达明显高于配对的正常组织,在 MDA-MB-231 细胞中的表达明显高于 MCF7 细胞。miR-182 敲低抑制了 MDA-MB-231 细胞的增殖和迁移,而 miR-182 过表达则显著促进了 MCF7 细胞的增殖和迁移。此外,FOXF2 被鉴定为 miR-182 的直接靶标。我们的研究结果表明,miR-182 可能通过下调 FOXF2 促进 TNBC 细胞的增殖和迁移。miR-182 可能成为 TNBC 治疗的潜在靶点。

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