MiR-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1
MiR-34a inhibits proliferation and migration of breast cancer through down-regulation of Bcl-2 and SIRT1
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MiR-34a通过下调Bcl-2和SIRT1抑制乳腺癌的增殖和迁移
DOI：
10.1007/s10238-012-0186-5
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发表时间：
2013-05-01
影响因子：
4.6
通讯作者：
Xie, Xiaoming
中科院分区：
文献类型：
--
作者：
Li, Laisheng;Yuan, Linjin;Xie, Xiaoming
MicroRNA-34a（miR-34a）是p53网络的关键成员，被发现在多种类型的肿瘤中下调，并进一步报道为肿瘤抑制microRNA。然而，miR-34a 在乳腺癌中的概况和生物学效应仍不清楚。在本研究中，我们旨在确定 miR-34a 对乳腺癌生长的影响，并探讨其效果是否是通过靶向 Bcl-2 和 SIRT1 来实现的。我们通过 qRT-PCR 检测了乳腺癌细胞系和乳腺癌样本中的 miR-34a 水平。通过增殖测定、凋亡测定和形态学监测来评估 miR-34a 在乳腺癌细胞系中的肿瘤抑制作用。 Western blotting 用于鉴定 miR-34a 的靶标。我们还研究了 miR-34a 与 5-FU 联合治疗对乳腺癌细胞的抗肿瘤作用。我们发现，与永生化正常乳腺上皮细胞系 184A1 相比，5 个乳腺癌细胞系中 miR-34a 的表达下调，并且与相应的邻近非恶性乳腺组织相比，乳腺癌样本中 miR-34a 的表达也下调了近 50%。乳腺癌细胞中 miR-34a 的异位恢复抑制了细胞增殖、侵袭并诱导细胞凋亡。 Bcl-2和SIRT1作为miR-34a的靶标被发现与miR-34a的异位表达呈负相关。此外，miR-34a 与 5-FU 联合治疗比 miR-34a 或 5-FU 单独治疗显着显示出更有效的抗肿瘤作用。由于 miR-34a 在乳腺癌中起到肿瘤抑制 microRNA 的作用，因此调节乳腺癌中的 miR-34a 水平被认为是一种新的、有用的乳腺癌治疗方法。
MicroRNA-34a(miR-34a), a pivotal member of the p53 network, was found to be down-regulated in multiple types of tumors and further reported as a tumor suppressor microRNA. However, the profile and biological effects of miR-34a in breast cancer are still unclear. In this study, we aimed to determine the effect of miR-34a on the growth of breast cancer and to investigate whether its effect is achieved by targeting Bcl-2 and SIRT1. We examined miR-34a levels in breast cancer cell lines and breast cancer specimens by qRT-PCR. Proliferation assay, apoptosis assay, and morphological monitoring were performed to assess the tumor suppression effect of miR-34a in breast cancer cell lines. Western blotting was used to identify the targets of miR-34a. We also investigated the anti-tumor effects of the treatment combining miR-34a with 5-FU in breast cancer cells. We found that miR-34a expression was down-regulated in 5 breast cancer cell lines compared with the immortalized normal mammary epithelial cell line 184A1, and was also down-regulated by almost 50 % in breast cancer samples compared with their corresponding adjacent non-malignant breast tissues. Ectopic restoration of miR-34a in breast cancer cells suppressed cells proliferation, invasion, and induced apoptosis. Bcl-2 and SIRT1 as the targets of miR-34a were found to be in reverse correlation with ectopic expression of miR-34a. Furthermore, the treatment combining miR-34a with 5-FU significantly showed more efficient anti-tumor effects than single treatment of miR-34a or 5-FU. Since miR-34a functions as tumor suppressor microRNA in breast cancer, modulating miR-34a level in breast cancer was suggested to be a new and useful approach of breast cancer therapy.