Related Experiment Video

Updated: Aug 8, 2025

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
10:13

Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice

Published on: August 12, 2014

13.5K

Loss of p53 Concurrent with RAS and TERT Activation Induces Glioma Formation

Meiting Gong1,2, Xiaoqing Fan3,4, Huihan Yu1

  • 1Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, No. 81, Meishan Road, Hefei, 230032, Anhui, China.

Molecular Neurobiology
|March 3, 2023
PubMed

Insights

Glioma development involves genetic changes in neural stem cells (NSCs). Specific mutations (RAS, TERT, p53) and EZH2 palmitoylation drive malignant transformation, impacting key molecular pathways.

Area of Science:

  • Neuroscience
  • Oncology
  • Molecular Biology

Background:

  • The origin of gliomas, a type of brain tumor, is debated, with theories focusing on functional or genetic alterations in neural stem cells (NSCs).
  • Advances in genetic engineering allow for the creation of NSC-based glioma models that mimic human tumor pathology.

Purpose of the Study:

  • To investigate the genetic and molecular mechanisms underlying glioma development in neural stem cells.
  • To identify key oncogenes and molecular pathways involved in the malignant transformation of NSCs.

Main Methods:

  • Utilized a mouse tumor transplantation model with genetically engineered neural stem cells.
  • Analyzed the roles of RAS, TERT, and p53 mutations/expression in glioma occurrence.
  • Investigated the mechanism of EZH2 palmitoylation mediated by ZDHHC5.

Main Results:

  • RAS, TERT, and p53 mutations/abnormal expression were linked to glioma formation.
  • EZH2 palmitoylation, facilitated by ZDHHC5, was crucial for malignant transformation.
  • EZH2 palmitoylation led to increased H3K27me3, decreased miR-1275, elevated GFAP, and reduced DNMT3A binding to the OCT4 promoter.

Conclusions:

  • Specific oncogenes (RAS, TERT, p53) in human NSCs promote rapid malignant transformation.
  • Gene alterations combined with susceptible cell types are critical determinants for glioma occurrence.
  • The EZH2 palmitoylation pathway represents a significant mechanism in glioma pathogenesis.
Keywords:
EZH2GliomagenesisRASTERTp53

More Related Videos

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells12:52

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells

Published on: November 28, 2015

15.9K
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.8K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
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,...
4.2K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.0K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.1K
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...
3.8K