In:
Cell Transplantation, SAGE Publications, Vol. 23, No. 4-5 ( 2014-05), p. 669-690
Abstract:
Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133 + cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133 + ) cells are still unclear. We have previously shown that ATRT-CD133 + cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133 + cells than in ATRT-CD133 - cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133 + cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133 - cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells.
Type of Medium:
Online Resource
ISSN:
0963-6897
,
1555-3892
DOI:
10.3727/096368914X678364
Language:
English
Publisher:
SAGE Publications
Publication Date:
2014
detail.hit.zdb_id:
2020466-8
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