文章：

STAT3通过抑制DAPK1调控miR93介导的肾细胞癌细胞凋亡

STAT3 regulates miR93-mediated apoptosis through inhibiting DAPK1 in renal cell carcinoma 

原文发布日期：2020-11-23 

英文摘要：

Signal transducer and activator of transcription 3 (STAT3) is an essential member of the STAT family. STAT3 regulates diverse genes that mediate inflammatory reactions, cell survival, proliferation, and angiogenesis, and it is aberrantly upregulated and activated in various types of malignancies. Furthermore, STAT3 signalling is involved in multiple feedback loops and pathways. In this study, we demonstrate that miR-93-3p plays an oncogenic role in renal cell carcinoma (RCC) by enhancing RCC cell proliferation and suppressing apoptosis. In addition, STAT3 can regulate the transcription of miR-93 by directly binding its promoter region. miR-93 can inhibit death-associated protein kinase 1 (DAPK1) at the protein level. Moreover, STAT3 can block DAPK1 expression at the RNA level. Importantly, we verified that DAPK1 overexpression in turn suppresses the entry of activated STAT3 into the cell nucleus. Thus, this study reveals a potential continuously activated signalling transduction pathway, STAT3-miR93-DAPK1, and may provide a novel clinical therapeutic approach for RCC. 

摘要翻译： 

信号转导与转录激活因子3（STAT3）是STAT家族的重要成员。它通过调控多种介导炎症反应、细胞存活、增殖和血管生成的基因，在多种恶性肿瘤中异常上调和激活。此外，STAT3信号通路参与多个反馈环路和调控网络。本研究发现miR-93-3p通过增强肾细胞癌（RCC）细胞增殖并抑制细胞凋亡，在RCC中发挥致癌作用。STAT3可直接结合miR-93启动子区域调控其转录，而miR-93能在蛋白水平抑制死亡相关蛋白激酶1（DAPK1）的表达。值得注意的是，STAT3还能在RNA水平抑制DAPK1的表达。更重要的是，我们证实过表达DAPK1会反向抑制活化STAT3的入核转运。因此，本研究揭示了一个可能持续激活的信号转导通路STAT3-miR93-DAPK1，为RCC的临床治疗提供了新思路。

原文链接：

STAT3 regulates miR93-mediated apoptosis through inhibiting DAPK1 in renal cell carcinoma