EGF Decreases the Abundance of MicroRNAs That Restrain Oncogenic Transcription Factors
EGF Decreases the Abundance of MicroRNAs That Restrain Oncogenic Transcription Factors
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DOI：
10.1126/scisignal.2000876
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发表时间：
2010-06-01
影响因子：
7.3
通讯作者：
Yarden, Yosef
中科院分区：
文献类型：
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作者：
Avraham, Roi;Sas-Chen, Aldema;Yarden, Yosef
表皮生长因子（EGF）通过启动在癌症中经常失调的基因表达程序来刺激细胞。通过结合信使RNA中的互补区域来减弱基因表达的微小RNA与癌症广泛相关。使用全基因组方法，我们发现EGF刺激启动了microRNA和转录因子的协调转录程序。最早的事件涉及23种微小RNA子集的丰度下降。这一步允许快速诱导致癌转录因子，如c-FOS，由立即早期基因编码。与作为EGF受体（EGFR）信号转导抑制剂的作用一致，我们报告说，这种早期microRNA子集的丰度在乳腺癌和由EGFR或密切相关的HER 2驱动的脑肿瘤中减少。这些发现确定了特定的microRNA作为生长因子信号传导和肿瘤发生的衰减剂。
Epidermal growth factor (EGF) stimulates cells by launching gene expression programs that are frequently deregulated in cancer. MicroRNAs, which attenuate gene expression by binding complementary regions in messenger RNAs, are broadly implicated in cancer. Using genome-wide approaches, we showed that EGF stimulation initiates a coordinated transcriptional program of microRNAs and transcription factors. The earliest event involved a decrease in the abundance of a subset of 23 microRNAs. This step permitted rapid induction of oncogenic transcription factors, such as c-FOS, encoded by immediate early genes. In line with roles as suppressors of EGF receptor (EGFR) signaling, we report that the abundance of this early subset of microRNAs is decreased in breast and in brain tumors driven by the EGFR or the closely related HER2. These findings identify specific microRNAs as attenuators of growth factor signaling and oncogenesis.