MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors

Cell Transplant. 2014;23(4-5):669-90. doi: 10.3727/096368914X678364.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism
  • Adolescent
  • Animals
  • Antigens, CD / metabolism
  • Base Sequence
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Cell Movement
  • Cell Survival / radiation effects
  • Child
  • Child, Preschool
  • Down-Regulation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Female
  • Gamma Rays
  • Glycoproteins / metabolism
  • Humans
  • Infant
  • Male
  • Medulloblastoma / genetics
  • Medulloblastoma / pathology
  • Medulloblastoma / radiotherapy*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism
  • Peptides / metabolism
  • Radiation, Ionizing
  • Tumor Cells, Cultured


  • AC133 Antigen
  • Adenylyl Cyclase Inhibitors
  • Antigens, CD
  • Glycoproteins
  • MIRN142 microRNA, human
  • MicroRNAs
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Adenylyl Cyclases
  • adenylate cyclase 9