Upregulation of mir-221 and mir-222 in atypical teratoid/rhabdoid tumors: potential therapeutic targets

Childs Nerv Syst. 2010 Mar;26(3):279-83. doi: 10.1007/s00381-009-1028-y. Epub 2009 Dec 10.

Abstract

Purpose: The aim of this study is to search for new therapeutic targets for atypical teratoid-rhabdoid tumors (ATRT).

Methods: To achieve this, we compared the expression of 365 microRNAs among ATRT, medulloblastomas, and normal brain.

Results: MiR-221 and miR-222 were within the top differentially expressed microRNAs. The deregulated expression of miR221/222 was demonstrated to inhibit the expression of the tumor suppressor and inhibitor of cell cycle p27(Kip1). Here, we demonstrated the negative regulation of p27(Kip1) by miR-221/222 in ATRT using microarray, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry.

Conclusion: As anti-miR therapy was recently proposed as an alternative treatment for cancer, these findings suggest that anti-miR-221/222 therapy might have therapeutic potential in ATRT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Male
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhabdoid Tumor / drug therapy
  • Rhabdoid Tumor / metabolism*
  • SMARCB1 Protein
  • Teratoma / drug therapy
  • Teratoma / metabolism*
  • Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • Cyclin-Dependent Kinase Inhibitor p27