MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation.
MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation.
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DOI：
10.1038/srep05908
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发表时间：
2014-08-01
影响因子：
4.6
通讯作者：
Lai LC
中科院分区：
文献类型：
--
作者：
Luo EC;Chang YC;Sher YP;Huang WY;Chuang LL;Chiu YC;Tsai MH;Chuang EY;Lai LC
缺氧和复氧是实体瘤的共同特征，导致氧化应激和应激反应基因的激活。以前，我们观察到N-myc下游调节基因1（NDRG 1）在转换为复氧后强烈下调，但NDRG 1的调控机制仍然难以捉摸。在这里，我们集中在NDRG 1的调控microRNAs（miRNAs）。将乳腺癌MCF-7细胞在缺氧下培养24小时，然后再给氧24小时。 通过Nanostring nCounter测定来检查miRNA谱。43种miRNAs在复氧后有显著变化。计算机模拟分析鉴定了四种氧敏感性miRNAs，其种子区域与NDRG 1的3′-UTR完全匹配。特别是，miR-769- 3 p能够抑制NDRG 1的表达，这导致复氧后NDRG 1蛋白的显著减少。此外，miR-769- 3 p的过表达显著抑制细胞增殖并增强细胞凋亡。我们的研究结果表明，miR-769- 3 p可以在氧浓度变化过程中功能调节NDRG 1。
Hypoxia and reoxygenation are common characteristics of solid tumors, which lead to oxidative stress and activation of stress-response genes. Previously, we observed that N-myc downstream-regulated gene 1 (NDRG1) was strongly down-regulated after shifting to reoxygenation, but the regulatory mechanism of NDRG1 remained elusive. Here we focused on the regulation of NDRG1 by microRNAs (miRNAs). Breast cancer MCF-7 cells were cultured under hypoxia for 24 h followed by 24 h of reoxygenation. The miRNA profiles were examined by Nanostring nCounter assays. Forty-three miRNAs had significant changes upon reoxygenation. In silico analysis identified four oxygen-sensitive miRNAs whose seed regions perfectly matched the 3′-UTR of NDRG1. In particular, miR-769-3p was able to inhibit the expression of NDRG1, which caused a significant reduction of NDRG1 protein upon reoxygenation. Furthermore, overexpression of miR-769-3p significantly inhibited cell proliferation and enhanced apoptosis. Our results revealed that miR-769-3p can functionally regulate NDRG1 during changes in oxygen concentration.
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影响因子：
14.9
作者：
Nygaard V;Hovig E
通讯作者：
Hovig E
影响因子：
2.7
作者：
Guimbellot JS;Erickson SW;Mehta T;Wen H;Page GP;Sorscher EJ;Hong JS
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影响因子：
2.1
作者：
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作者：
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作者：
Lai LC;Su YY;Chen KC;Tsai MH;Sher YP;Lu TP;Lee CY;Chuang EY
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