Related Experiment Videos

MicroRNA-21 expression is regulated by β-catenin/STAT3 pathway and promotes glioma cell invasion by direct targeting

Lei Han1, Xiao Yue, Xuan Zhou

  • 1Department of Neurosurgery, Tianjin Medical University General Hospital, China.

CNS Neuroscience & Therapeutics
|May 29, 2012
PubMed
Abstract

Insights

MicroRNA-21 (miR-21) drives glioma progression by promoting invasion and proliferation. Its expression is regulated by the β-catenin pathway via STAT3, offering a potential therapeutic target for glioma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-21 (miR-21) is upregulated in various human cancers, including glioma.
  • While miR-21's role in regulating glioma cell invasion via RECK is known, its transcriptional regulation remains unclear.

Purpose of the Study:

  • To elucidate the transcriptional regulation of miR-21 in glioma cells.
  • To investigate the role of the β-catenin and STAT3 pathways in miR-21 expression and its impact on glioma.

Main Methods:

  • Correlation analysis of miR-21 expression with glioma pathological grade.
  • Demonstration of β-catenin/STAT3-dependent regulation of miR-21 in cell lines.
  • Chromatin immunoprecipitation and luciferase reporter assays to identify STAT3 binding sites.
  • Xenograft model to assess the effect of miR-21 knockdown on tumor growth and invasion.

Main Results:

  • A positive correlation was found between miR-21 expression and glioma pathological grade.
  • The β-catenin pathway, dependent on signal transducer and activator of transcription 3 (STAT3), regulates miR-21 expression.
  • STAT3 directly binds to the miR-21 promoter, controlling its transcription.
  • miR-21 knockdown reduced glioma cell invasion by upregulating RECK and decreased tumor growth in vivo.

Conclusions:

  • β-catenin-mediated regulation of miR-21 through STAT3 is crucial for glioma cell invasion and proliferation.
  • Signal transducer and activator of transcription 3 (STAT3) represents a promising therapeutic target for glioma treatment.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...