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

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.