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DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC

Wenxi Yu1, Lina Tang1, Feng Lin1

  • 1Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.

Frontiers in Oncology
|January 22, 2019
PubMed

Insights

Diacylglycerol kinase zeta (DGKZ) acts as an oncogene in osteosarcoma, promoting tumor growth. Silencing DGKZ inhibits osteosarcoma cell proliferation and tumor growth by affecting the MYC pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Osteosarcoma (OS) is a primary bone cancer with limited treatment options, especially for metastatic cases.
  • Identifying novel therapeutic targets is crucial for improving osteosarcoma patient outcomes.
  • The role of Diacylglycerol kinase zeta (DGKZ) in osteosarcoma proliferation remains largely unknown.

Purpose of the Study:

  • To investigate the role of DGKZ in osteosarcoma.
  • To determine if DGKZ expression correlates with patient prognosis.
  • To elucidate the molecular mechanisms by which DGKZ influences osteosarcoma growth.

Main Methods:

  • DGKZ expression analysis in OS tumor samples.
  • In vitro studies using shRNA to silence DGKZ in osteosarcoma cells.
  • In vivo xenograft studies with DGKZ knockout.
  • Gene expression profiling using Affymetrix GeneChip and Ingenuity Pathway Analysis (IPA).
  • Protein-protein interaction studies using immunoprecipitation coupled with mass spectrometry (IP-MS).

Main Results:

  • DGKZ expression was elevated in OS tumors and associated with poor prognosis.
  • DGKZ silencing inhibited osteosarcoma cell growth and induced apoptosis in vitro.
  • DGKZ knockout suppressed tumor growth in vivo.
  • DGKZ knockdown led to decreased MYC pathway activity, altering target genes like CCND1, CDKN2B, CDK6, PCNA, and EGR1.
  • DGKZ was found to interact with ERK1/2, a known MYC pathway component.

Conclusions:

  • DGKZ functions as an oncogene in osteosarcoma.
  • DGKZ promotes osteosarcoma proliferation, potentially through interaction with ERK1/2 and modulation of the MYC pathway.
  • DGKZ represents a potential therapeutic target for osteosarcoma treatment.
Keywords:
DGKZERK1/2MYConcogeneosteosarcoma

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