Abstract
Abstract MicroRNA-200 (miR-200) family members suppress the epithelial-mesenchymal transition of various cancer cells, including lung adenocarcinoma cells. Previously, we found that forced expression of miR-200 decreased bone morphogenetic protein 4 (BMP4). In this study, we explored the mechanism and role of BMP4 depletion by miR-200 in murine lung adenocarcinoma cells. miR-200 down-regulated BMP4 via direct targeting of the GATA4 and GATA6 transcription factors that stimulate Bmp4 transcription. Bmp4 knockdown suppressed cancer cell growth, migration, and invasion and inhibited tumorigenesis and metastasis of lung cancer cells when injected into syngeneic mice. In addition, BMP4 was required for normal sphere formation in Matrigel 3-D culture, which might be mediated by MYH10, a downstream target of BMP4. These findings suggest that BMP4 functions as a pro-tumorigenic factor in a murine lung cancer model, and its transcription is regulated by miR-200 and GATA4/6. Citation Format: Jeong Seon Kim, Jonathan M. Kurie, Young-Ho Ahn. Lung tumorigenesis and metastasis is suppressed by the miR-200-GATA4/6-BMP4 axis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1908.
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