Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Sci Signal. 2010 Jun 1;3(124):ra43. doi: 10.1126/scisignal.2000876.
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.
表皮生长因子（EGF）通过启动基因表达程序刺激细胞，这些程序在癌症中经常失调。MicroRNAs 通过结合信使 RNA 中的互补区域来减弱基因表达，广泛参与癌症。我们使用全基因组方法表明，EGF 刺激引发了 microRNAs 和转录因子的协调转录程序。最早的事件涉及一组 23 个 microRNAs 的丰度降低。这一步骤允许立即早期基因编码的致癌转录因子，如 c-FOS 的快速诱导。与作为 EGF 受体（EGFR）信号的抑制剂的作用一致，我们报告说，由 EGFR 或密切相关的 HER2 驱动的乳腺癌和脑肿瘤中，这一早期 microRNAs 子集的丰度降低。这些发现确定了特定的 microRNAs 作为生长因子信号和致癌作用的抑制剂。
