Abstract 2042: Aberrant expression of miR-21 triggers malignancy of human gliomas by disrupting negative feedback regulator, Spry2

Abstract

Abstract The malignant progression of glioma is accompanied by diffuse infiltration. Recent evidences suggest the significant role of microRNAs in cancer cell migration and invasion. Therefore, we hypothesized that deregulation of microRNA may be important for the malignant progression of glioma. We found that aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional PTEN, but not wild-type PTEN-harboring glioma cells. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues as well as cancer stem cell-derived tumor models, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, although they were inversely correlated with miR-21. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 plays an essential role on the malignant progression of human gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2042.