Grade-specific expression profiles of miRNAs/mRNAs and docking study in human grade I-III astrocytomas

OMICS. 2011 Oct;15(10):673-82. doi: 10.1089/omi.2011.0064.

Abstract

Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Astrocytoma / genetics*
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Computer Simulation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • Male
  • Metabolic Networks and Pathways / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Models, Genetic
  • Neoplasm Grading
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism*
  • Signal Transduction / genetics

Substances

  • MIRN124 microRNA, human
  • MIRN149 microRNA, human
  • MicroRNAs
  • RNA, Messenger