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NSD2 activates the E2F transcription factor 1/Y-box binding protein 2 axis to promote the malignant development of

Lili Zhang1, Guangyao Hu1

  • 1Department of Stomatology, Affiliated Hospital of Beihua University, Jilin 132011, Jilin, PR China.

Archives of Oral Biology
|April 1, 2022
PubMed
Abstract

Insights

Nuclear receptor-binding SET domain protein 2 (NSD2) promotes oral squamous cell carcinoma (OSCC) by activating E2F1 and YBX2. Silencing NSD2, E2F1, or YBX2 may inhibit OSCC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Nuclear receptor-binding SET domain protein 2 (NSD2) is a histone methyltransferase implicated in cancer.
  • Its role in oral squamous cell carcinoma (OSCC) requires further investigation.

Purpose of the Study:

  • To investigate the role of NSD2 and its downstream molecules in OSCC.
  • To explore NSD2's mechanism of action in OSCC progression.

Main Methods:

  • Analysis of OSCC dataset (GSE138206) to identify key genes.
  • Examination of NSD2 expression in OSCC tissues and cells.
  • In vitro and in vivo functional assays following NSD2 silencing.
  • Bioinformatic prediction and rescue experiments for downstream molecules E2F1 and YBX2.

Main Results:

  • NSD2 and H3K36me2 were upregulated in OSCC.
  • NSD2 silencing inhibited OSCC cell proliferation, invasion, and epithelial-mesenchymal transition, while inducing apoptosis and reducing tumor growth.
  • NSD2 silencing suppressed E2F1 transcription via H3K36me2 inhibition at the E2F1 promoter.
  • E2F1 transcriptionally activated YBX2; E2F1 or YBX2 upregulation rescued OSCC phenotypes suppressed by NSD2 silencing.

Conclusions:

  • NSD2 acts as an oncogene in OSCC by activating the E2F1/YBX2 axis.
  • Targeting NSD2, E2F1, or YBX2 presents a potential therapeutic strategy for OSCC.
Keywords:
E2F transcription factor 1NSD2Oral squamous cell carcinomaY-box binding protein 2

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