Related Experiment Video

Updated: Sep 16, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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The small GTP-binding Ras-like protein DIRAS2 promotes cell proliferation in oral leukoplakia via the RAF/MEK/MAPK

Jing Li1, Zitong Tian2, Wenjing Li2

  • 1Beijing Institute of Dental Research, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Fengtai District, Beijing 100070, China; Department of Stomatology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China.

Tissue & Cell
|July 11, 2025
PubMed
Abstract

Insights

DIRAS2, a Ras-like protein, is overexpressed in oral leukoplakia. Its removal in mouse epithelium inhibits precancer progression by reducing cell proliferation via the RAF/MEK/MAPK pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The small GTP-binding protein DIRAS2 is implicated as a potential tumor suppressor.
  • Its role in precancerous lesions and cancer progression is not well understood.

Purpose of the Study:

  • To investigate the role of DIRAS2 in oral precancerous lesions.
  • To explore the mechanism by which DIRAS2 influences cancer progression.

Main Methods:

  • DIRAS2 expression analysis in human oral leukoplakia (OLK) and normal tissues.
  • Generation of DIRAS2 conditional knockout mice using CRISPR/Cas9 and Cre-LoxP technology.
  • 4-Nitroquinoline 1-oxide (4NQO) induced tongue precancerous lesion model in mice.

Main Results:

  • DIRAS2 expression was significantly higher in human OLK tissues compared to normal tissues.
  • Epithelial DIRAS2 knockout inhibited 4NQO-induced tongue precancerous lesion progression in mice.
  • DIRAS2 knockdown/knockout reduced cell proliferation and downregulated MAPK signaling pathway proteins.

Conclusions:

  • DIRAS2 is upregulated in oral leukoplakia and promotes cell proliferation.
  • DIRAS2 may drive oral precancer progression through the RAF/MEK/MAPK pathway.
Keywords:
Conditional-knockout miceDIRAS2MAPKOLKProliferation

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