Du Yang, Kong Chuize
Department of Urology, First Hospital of China Medical University, 110001, Shenyang, China.
Cancer Gene Ther. 2021 May;28(5):502-513. doi: 10.1038/s41417-020-00235-y. Epub 2020 Nov 23.
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.
信号转导与转录激活因子3（STAT3）是STAT家族的重要成员。STAT3调控多种介导炎症反应、细胞存活、增殖和血管生成的基因，并且在各种类型的恶性肿瘤中异常上调和激活。此外，STAT3信号传导涉及多个反馈回路和途径。在本研究中，我们证明miR-93-3p通过增强肾细胞癌（RCC）细胞增殖和抑制凋亡在RCC中发挥致癌作用。此外，STAT3可通过直接结合其启动子区域来调控miR-93的转录。miR-93可在蛋白质水平抑制死亡相关蛋白激酶1（DAPK1）。此外，STAT3可在RNA水平阻断DAPK1的表达。重要的是，我们证实DAPK1的过表达反过来会抑制激活的STAT3进入细胞核。因此，本研究揭示了一条潜在的持续激活的信号转导途径，即STAT3-miR93-DAPK1，并可能为RCC提供一种新的临床治疗方法。
