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微小RNA-409-5p在乳腺癌中上调,其下调通过RSU1的下游靶点抑制癌症发展。

MicroRNA-409-5p is upregulated in breast cancer and its downregulation inhibits cancer development through downstream target of RSU1.

作者信息

Yu Hong, Xing Hua, Han Wei, Wang Yali, Qi Tianyang, Song Changlong, Xu Zheli, Li Hongjun, Huang Yinghui

机构信息

1 Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

2 Department of Hematology, Cancer Center, The First Hospital of Jilin University, Changchun, China.

出版信息

Tumour Biol. 2017 May;39(5):1010428317701647. doi: 10.1177/1010428317701647.

Abstract

We investigated the expression and function of miR-409-5p in human breast cancer. Quantitative real-time polymerase chain reaction was conducted to evaluate endogenous miR-409-5p expression in breast cancer tumors and breast cancer cell lines. Lentiviral transduction was performed to stably downregulate miR-409-5p in breast cancer cell lines MDA-MB-231 and MCF-7 and cells. The effects of miR-409-5p downregulation on breast cancer proliferation, migration, and xenograft development were then evaluated. Downstream target gene of miR-409-5p, Ras suppressor protein 1, was examined by dual-luciferase activity assay, quantitative real-time polymerase chain reaction, and western blot in lentiviral-transduced breast cancer cells. Ras suppressor protein 1 was also inhibited in miR-409-5p-downregulated breast cancer cells to examine its functional effect on breast cancer proliferation and migration. MiR-409-5p was aberrantly upregulated in both breast cancer tumors and cell lines. Lentiviral transduction successfully downregulated endogenous miR-409-5p expression as well as suppressed proliferation, migration, and xenograft development in MDA-MB-231 and MCF-7 cells. Ras suppressor protein 1 was confirmed to be directly targeted by miR-409-5p in breast cancer cells. Small interfering RNA-mediated Ras suppressor protein 1 inhibition reversely promoted cancer proliferation and migration in miR-409-5p-downregualted breast cancer cells. MiR-409-5p is downregulated in breast cancer and its inhibition has anti-cancer effect on breast cancer development both in vitro and in vivo. The regulatory effect of miR-409-5p inhibition is likely through the inverse upregulation of Ras suppressor protein 1 in breast cancer.

摘要

我们研究了miR-409-5p在人类乳腺癌中的表达及功能。采用定量实时聚合酶链反应来评估乳腺癌肿瘤组织和乳腺癌细胞系中内源性miR-409-5p的表达。通过慢病毒转导在乳腺癌细胞系MDA-MB-231和MCF-7及细胞中稳定下调miR-409-5p。随后评估miR-409-5p下调对乳腺癌增殖、迁移及异种移植瘤生长的影响。通过双荧光素酶活性测定、定量实时聚合酶链反应及蛋白质免疫印迹法检测慢病毒转导的乳腺癌细胞中miR-409-5p的下游靶基因——Ras抑制蛋白1。在miR-409-5p下调的乳腺癌细胞中也抑制Ras抑制蛋白1,以检测其对乳腺癌增殖和迁移的功能影响。miR-409-5p在乳腺癌肿瘤组织和细胞系中均异常上调。慢病毒转导成功下调了内源性miR-409-5p的表达,并抑制了MDA-MB-231和MCF-7细胞的增殖、迁移及异种移植瘤生长。在乳腺癌细胞中证实Ras抑制蛋白1是miR-409-5p的直接靶标。小干扰RNA介导的Ras抑制蛋白1抑制在miR-409-5p下调的乳腺癌细胞中反向促进了肿瘤的增殖和迁移。miR-409-5p在乳腺癌中表达下调,其抑制对乳腺癌的体外和体内发展均具有抗癌作用。miR-409-5p抑制的调节作用可能是通过在乳腺癌中反向上调Ras抑制蛋白1来实现的。

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