MicroRNA-20b promotes cell proliferation via targeting of TGF-β receptor II and upregulates MYC expression in Ewing's sarcoma cells.

Abstract

Transforming growth factor-β receptor II (TGFBR2) is implicated in various types of cancer. Most molecules involved in the TGF-β pathway can be degraded by one or more microRNAs (miRNAs). In the present study, we show that miRNA plays an important role in downregulating TGFBR2 expression in Ewing's sarcoma (ES) cells. Microarray-based analyses revealed that the expression of miR-20b was significantly increased, whereas TGFBR2 and MYC were significantly downregulated and upregulated, respectively, in all ES cells compared to their expression in human mesenchymal stem cells (hMSCs). In ES cell lines, anti-miR-20b increased TGFBR2 expression and significantly decreased MYC expression, showing an inverse relationship with TGFBR2. The induction by anti-miR-20b further prohibited ES cell growth and cell cycle progression. Moreover, decreased miR-20b in ES cells significantly inhibited tumor growth invivo. Taken together, these results suggest that miR-20b behaves as an oncogene in ES when its overexpression is unregulated by targeting TGFBR2. Because downstream TGFBR2 and TGF-β signaling regulate cell cycle, apoptosis, and tumor proliferation via MYC, our findings may contribute to new targeted therapies for ES.