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miR-103 通过靶向嗅觉受体蛋白 4 调节三阴性乳腺癌细胞的迁移和侵袭。

miR-103 regulates triple negative breast cancer cells migration and invasion through targeting olfactomedin 4.

机构信息

Surgery Teaching and Research Section, Clinical Medical School, Jining Medical University, NO. 16 Hehua Road, Jining, Shandong 272067, China.

Academy of Basic Medicine, Jining Medical University, NO. 16 Hehua Road, Jining, Shandong 272067, China.

出版信息

Biomed Pharmacother. 2017 May;89:1401-1408. doi: 10.1016/j.biopha.2017.02.028. Epub 2017 Mar 19.

Abstract

Our previous study showed olfactomedin 4 (OLFM4) suppressed triple-negative breast cancer cells migration, invasion and metastasis-associated protein MMP 9 expression. OLFM4 was identified as a potential target of miR-103 according to microRNA target databases and published studies. The aim of this study is to validate the relationship between miR-103 and OLFM4, and explore the function and clinical significance of miR-103 in triple-negative breast cancer patients. In our results, miR-103 negatively regulated OLFM4 expression by directly targeting its 3'-UTR. OLFM4 was a functional target of miR-103 to regulate triple-negative breast cancer cells migration, invasion and MMP 9 expression. Moreover, miR-103 overexpression was observed in triple-negative breast cancer tissues and cell lines, and associated with lymph node metastasis, distant metastasis and clinical stage. Univariate and multivariate analyses suggested that miR-103 overexpression was a poor independent prognostic factor for triple-negative breast cancer patients. In conclusion, miR-103 acts as an oncogene miRNA to promote triple-negative breast cancer cells migration and invasion through targeting OLFM4.

摘要

我们之前的研究表明,嗅觉素 4(OLFM4)抑制三阴性乳腺癌细胞迁移、侵袭和转移相关蛋白 MMP9 的表达。根据 microRNA 靶标数据库和已发表的研究,OLFM4 被确定为 miR-103 的潜在靶标。本研究旨在验证 miR-103 与 OLFM4 之间的关系,并探讨 miR-103 在三阴性乳腺癌患者中的功能和临床意义。在我们的研究结果中,miR-103 通过直接靶向其 3'UTR 负调控 OLFM4 的表达。OLFM4 是 miR-103 调节三阴性乳腺癌细胞迁移、侵袭和 MMP9 表达的功能靶标。此外,在三阴性乳腺癌组织和细胞系中观察到 miR-103 的过表达,并与淋巴结转移、远处转移和临床分期相关。单因素和多因素分析表明,miR-103 过表达是三阴性乳腺癌患者不良的独立预后因素。综上所述,miR-103 通过靶向 OLFM4 作为一种癌基因 miRNA 促进三阴性乳腺癌细胞的迁移和侵袭。

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