Tsai Yuan-Chin, Chen Wei-Yu, Siu Man Kit, Tsai Hong-Yuan, Yin Juan Juan, Huang Jiaoti, Liu Yen-Nien
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Cancer Lett. 2017 Jan 1;384:1-8. doi: 10.1016/j.canlet.2016.10.014. Epub 2016 Oct 13.
It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulation. In addition, EGFR acts as a transcriptional coactivator that binds to the promoter of primary miR-96 and transcriptionally regulates miR-96 levels. We analyzed two sets of clinical prostate cancer samples, confirmed association patterns that were consistent with the EGFR-miR-96-ETV6 signaling model and demonstrated that the reduced ETV6 levels were associated with malignant prostate cancer. Based on results derived from multiple approaches, we identified the biological functions of ETV6 as a tumor suppressor that inhibits proliferation and metastasis in prostate cancer. We present a molecular mechanism in which EGFR activation leads to the induction of miR-96 expression and suppression of ETV6, which contributes to prostate cancer progression.
有人提出ETV6作为一种肿瘤抑制因子；然而，其分子调控和细胞功能仍不清楚。我们以前列腺癌为模型系统，证明了一种分子机制，即表皮生长因子受体（EGFR）信号可通过微小RNA-96（miR-96）介导的下调来调控ETV6。此外，EGFR作为一种转录共激活因子，与初级miR-96的启动子结合并转录调控miR-96水平。我们分析了两组临床前列腺癌样本，证实了与EGFR-miR-96-ETV6信号模型一致的关联模式，并证明ETV6水平降低与恶性前列腺癌相关。基于多种方法得出的结果，我们确定了ETV6作为一种肿瘤抑制因子的生物学功能，其可抑制前列腺癌的增殖和转移。我们提出了一种分子机制，即EGFR激活导致miR-96表达的诱导和ETV6的抑制，这促进了前列腺癌的进展。
