MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes

Yunqing Li1, Fadila Guessous, Ying Zhang

  • 1Departments of Microbiology, Neurology and Pathology, University of Virginia, Charlottesville, VA 22908, USA.

Cancer Research
|September 24, 2009
PubMed

Insights

MicroRNA-34a (miR-34a) suppresses brain tumor growth by targeting c-Met and Notch signaling pathways. Down-regulation of miR-34a correlates with glioblastoma, suggesting its therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-34a (miR-34a) is a p53 target gene with reduced expression in certain cancers.
  • The role of miR-34a in brain tumors, particularly gliomas, requires comprehensive investigation.

Purpose of the Study:

  • To investigate the expression, targets, and functional impact of miR-34a in brain tumor cells and human gliomas.
  • To determine if miR-34a can be a potential therapeutic agent for brain tumors.

Main Methods:

  • Studied miR-34a expression and its effects on target genes (c-Met, Notch-1, Notch-2, CDK6) in glioma and medulloblastoma cell lines.
  • Utilized reporter assays, analyzed human glioma specimens, and performed in vivo xenograft studies.
  • Investigated the reversal of miR-34a effects by forced expression of target genes.

Main Results:

  • miR-34a down-regulated c-Met, Notch-1, Notch-2, and CDK6 protein expression.
  • miR-34a expression inhibited reporter activities for c-Met and Notch signaling.
  • Down-regulated miR-34a levels were observed in glioblastoma tissues and mutant p53 gliomas, inversely correlating with c-Met levels.
  • miR-34a transfection inhibited glioma cell proliferation, survival, and invasion, with no effect on normal astrocytes.
  • In vivo glioblastoma xenograft growth was significantly inhibited by miR-34a expression.

Conclusions:

  • miR-34a acts as a tumor suppressor in gliomas by targeting c-Met and Notch pathways.
  • miR-34a expression is reduced in human gliomas, correlating with tumor progression.
  • miR-34a holds promise as a potential therapeutic agent for brain tumors.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...