Abstract 3949: Microrna142 3p promotes tumorinitiating and radioresistant properties in malignant pediatric brain tumors

Abstract

Abstract Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) is an extremely malignant pediatric brain tumor in infancy and childhood. It has been reported that subpopulation of CD133+ cells isolated from ATRT tumors present cancer stem-like and radioresistant property. However, the exact biomolecular mechanism of ATRT or AT/RT-CD133+ is still unclear. In this study, we firstly showed that CD133-positive AT/RT cells (CD133+) have a pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). Using microRNA array and quantitative RT-PCR, our data showed that expression of miR142-3p was lower in AT/RT-CD133+ than in AT/RT-CD133−. MiR142-3p overexpression significantly inhibited self-renewal and tumorigenicity of AT/RT-CD133+. On the contrary, silencing of endogenous miR142-3p dramatically increased tumor-initiating and stem-like cell capacities in ATRT or AT/RT-CD133− cells, and further promoted the mesenchymal-transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted NOD-SCID mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant property of malignant pediatric brain cancer stem cells. Citation Format: Shih-Hwa Chiou. Microrna142 3p promotes tumorinitiating and radioresistant properties in malignant pediatric brain tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3949. doi:10.1158/1538-7445.AM2014-3949