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微小RNA-3941靶向胰岛素样生长因子-1以调节乳腺癌细胞的增殖和迁移。

MicroRNA-3941 targets IGF-1 to regulate cell proliferation and migration of breast cancer cells.

作者信息

Dang Xiangguo, Li Xiangqi, Wang Lin, Sun Xibo, Tian Xingsong

机构信息

Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.

Department of Breast Surgery, Affiliated Hospital of Taishan Medical University Taian 271000, Shandong, China.

出版信息

Int J Clin Exp Pathol. 2017 Jul 1;10(7):7650-7660. eCollection 2017.

Abstract

We aimed to investigate the effects and regulatory mechanism of microRNA-3941 (miR-3941) in the progression of breast cancer. The expression of miR-3941 and insulin-like growth factor 1 (IGF-1) was determined in breast cancer tissues and cell lines. A miR-3941 mimics, inhibitor, and scramble RNA were individually transfected into the cancer cells. Then, the effects of overexpression and suppression of miR-3941 on cell viability, migration, and invasion, as well as on the expression of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, and vimentin) were further investigated. In addition, luciferase reporter analysis was performed to confirm whether IGF-1 was the potential target of miR-3941. Small interfering RNA targeting IGF-1 was transfected into the cells to further investigate whether miR-3941 regulated the breast cancer cell migration and invasion by targeting IGF-1. The inverse expression of miR-3941 (downregulated) and IGF-1 (upregulated) was observed in the breast cancer tissues and cells. The overexpression of miR-3941 significantly inhibited the breast cancer cell viability and suppressed cell migration and invasion. In addition, IGF-1 was confirmed as the target of miR-3941, and IGF-1 expression was negatively regulated by miR-3941. The knockdown of IGF-1 significantly reversed the inhibitory effects of miR-3941 overexpression on cell migration, invasion, and the EMT-related proteins. Our results indicate that miR-3941 is downregulated in breast cancer cells, and the downregulation of miR-3941 may promote breast cancer cell proliferation, migration, and invasion through not targeting IGF-1 expression. miR-3941 and IGF-1 may serve as diagnostic markers or potential targets for breast cancer treatment.

摘要

我们旨在研究微小RNA-3941(miR-3941)在乳腺癌进展中的作用及调控机制。检测了miR-3941和胰岛素样生长因子1(IGF-1)在乳腺癌组织和细胞系中的表达。将miR-3941模拟物、抑制剂和乱序RNA分别转染至癌细胞中。随后,进一步研究了miR-3941过表达和抑制对细胞活力、迁移和侵袭以及上皮-间质转化(EMT)相关蛋白(E-钙黏蛋白、N-钙黏蛋白和波形蛋白)表达的影响。此外,进行荧光素酶报告基因分析以确认IGF-1是否为miR-3941的潜在靶标。将靶向IGF-1的小干扰RNA转染至细胞中,以进一步研究miR-3941是否通过靶向IGF-1来调节乳腺癌细胞的迁移和侵袭。在乳腺癌组织和细胞中观察到miR-3941(下调)和IGF-1(上调)的反向表达。miR-3941的过表达显著抑制了乳腺癌细胞活力,并抑制了细胞迁移和侵袭。此外,IGF-1被确认为miR-3941的靶标,且miR-3941对IGF-1表达具有负调控作用。IGF-1的敲低显著逆转了miR-3941过表达对细胞迁移、侵袭和EMT相关蛋白的抑制作用。我们的结果表明,miR-3941在乳腺癌细胞中表达下调,且miR-3941的下调可能通过不靶向IGF-1表达来促进乳腺癌细胞增殖、迁移和侵袭。miR-3941和IGF-1可能作为乳腺癌治疗的诊断标志物或潜在靶标。

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