Analysis of the function and mechanism of DIRAS1 in osteosarcoma

Huan Liu1, Weibin Shu2, Tianyue Liu1

  • 1Department of Osteology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Tissue & Cell
|April 12, 2022
PubMed
Abstract

Insights

DIRAS1, regulated by METTL3/METTL14, impacts osteosarcoma cell behavior by affecting the ERK pathway. This study reveals DIRAS1

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma is a common bone cancer known for lung metastasis.
  • The role of DIRAS family GTPase 1 (DIRAS1) in osteosarcoma remains unclear.

Purpose of the Study:

  • To investigate the function and mechanism of DIRAS1 in osteosarcoma.
  • To explore the regulatory relationship between DIRAS1, METTL3/METTL14, and the ERK pathway in osteosarcoma.

Main Methods:

  • Western blot and immunofluorescence were used to analyze DIRAS1 expression and localization.
  • Cell proliferation, invasion, migration, and apoptosis were assessed using various assays.
  • RNA interference and plasmid transfection modulated DIRAS1 expression.
  • Methylation levels (m6A) and protein expression (p-ERK, p-AKT) were quantified.
  • Rescue experiments evaluated the interplay between METTL3/METTL14 and DIRAS1.

Main Results:

  • DIRAS1 is localized in the nucleus of osteosarcoma cells.
  • DIRAS1 silencing enhanced proliferation, invasion, and migration while inhibiting apoptosis.
  • DIRAS1 regulated p-ERK expression but not p-AKT.
  • METTL3/METTL14 suppressed DIRAS1 expression.
  • METTL3/METTL14 reversed the effects of DIRAS1 overexpression on cell behavior and p-ERK levels.

Conclusions:

  • DIRAS1, modulated by METTL3 and METTL14, significantly influences osteosarcoma cell malignancy.
  • The ERK pathway is a key mediator in DIRAS1's effect on osteosarcoma progression.

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