Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells.
Expression of miR-34c induces G2/M cell cycle arrest in breast cancer cells.
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DOI：
10.1186/1471-2407-14-538
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发表时间：
2014-07-26
期刊：
影响因子：
3.8
通讯作者：
Larsson C
中科院分区：
文献类型：
--
作者：
Achari C;Winslow S;Ceder Y;Larsson C
MicroRNA-34是一个由三个miRNAs组成的家族，已被报道具有肿瘤抑制作用，并显示在各种癌症中表达降低。在这里，我们研究了miR-34c在基底样乳腺癌细胞中的功能。来自癌症基因组图谱(TCGA)的数据被用于评估原发性乳腺癌的表达。通过胸腺嘧啶核苷掺入、Annexin V分析和乳腺癌细胞系细胞周期分析，研究miR-34c对细胞进程的影响。用定量聚合酶链式反应和蛋白质印迹分析对潜在靶点的影响。TCGA结果显示miR-34c在基底细胞样癌中低水平表达，低表达与预后不良有关。异位表达miR-34c可抑制乳腺癌细胞增殖，增加细胞死亡。此外，miR-34c主要通过诱导细胞周期停滞于G2/M期而影响细胞周期。我们发现，已知的调控细胞周期的miR-34靶标CCND1、CDK4和CDK6的表达水平在乳腺癌细胞系miR-34c的表达下调。此外，在miR-34c表达后，有丝分裂过程中的重要调节因子CDC23的水平受到抑制，针对CDC23的siRNA模拟了miR-34c对G2/M期停滞的影响。然而，PRKCA的蛋白水平，一个预测的miR-34c靶点和一个已知的乳腺癌细胞增殖调节因子，不受miR-34c的影响。综上所述，我们的结果支持miR-34c作为肿瘤抑制因子miRNA在乳腺癌中的作用。本文的在线版本(DOI：10.1186/1471-2407-14-538)包含补充材料，可供授权用户使用。
MicroRNA-34 is a family of three miRNAs that have been reported to function as tumor suppressor miRNAs and show decreased expression in various cancers. Here, we examine functions of miR-34c in basal-like breast cancer cells. Data from The Cancer Genome Atlas (TCGA) were used for evaluation of expression in primary breast cancers. Cellular processes affected by miR-34c were investigated by thymidine incorporation, Annexin V-assays and cell cycle analysis using breast cancer cell lines. Effects on potential targets were analyzed with qPCR and Western blot. TCGA data revealed that miR-34c was expressed at lower levels in basal-like breast cancer tumors and low expression was associated with poor prognosis. Ectopic expression of miR-34c in basal-like breast cancer cell lines resulted in suppressed proliferation and increased cell death. Additionally, miR-34c influenced the cell cycle mainly by inducing an arrest in the G2/M phase. We found that expression levels of the known cell cycle-regulating miR-34 targets CCND1, CDK4 and CDK6, were downregulated upon miR-34c expression in breast cancer cell lines. In addition, the levels of CDC23, an important mediator in mitotic progression, were suppressed following miR-34c expression, and siRNAs targeting CDC23 mimicked the effect of miR-34c on G2/M arrest. However, protein levels of PRKCA, a predicted miR-34c target and a known regulator of breast cancer cell proliferation were not influenced by miR-34c. Together, our results support the role of miR-34c as a tumor suppressor miRNA also in breast cancer. The online version of this article (doi:10.1186/1471-2407-14-538) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
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影响因子：
64.8
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通讯作者：
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影响因子：
3.4
作者：
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影响因子：
4.6
作者：
Li, Laisheng;Yuan, Linjin;Xie, Xiaoming
通讯作者：
Xie, Xiaoming