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The clock gene PER1 suppresses expression of tumor-related genes in human oral squamous cell carcinoma

Han-Xue Li1, Xiao-Juan Fu1, Kai Yang1

  • 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

Oncotarget
|March 5, 2016
PubMed

Insights

The clock gene PER1 acts as a tumor suppressor. Knocking down PER1 in oral cancer cells accelerated tumor growth, invasion, and resistance to apoptosis, suggesting PER1 as a potential cancer treatment target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Chronobiology

Background:

  • Aberrant expression of the Period 1 (PER1) clock gene is linked to cancer development.
  • PER1's role in oral squamous cell carcinoma (OSCC) progression remains to be fully elucidated.

Purpose of the Study:

  • To investigate the functional role of PER1 in OSCC progression.
  • To evaluate PER1 as a potential therapeutic target in oral cancer.

Main Methods:

  • Designed short hairpin RNAs (shRNAs) to achieve PER1 knockdown in SCC15 human OSCC cells.
  • Assessed cellular behaviors including growth, proliferation, apoptosis resistance, migration, and invasion in vitro.
  • Quantified mRNA expression levels of key genes involved in cell cycle regulation, apoptosis, and metastasis.
  • Evaluated the effect of PER1 knockdown on tumor development in a xenograft mouse model.

Main Results:

  • PER1 knockdown significantly promoted SCC15 cell growth, proliferation, and resistance to apoptosis.
  • Knockdown cells exhibited enhanced migration and invasion capabilities.
  • PER1 knockdown altered the expression of oncogenes (e.g., KI-67, MDM2, BCL-2, MMP2, MMP9) and tumor suppressors (e.g., C-MYC, p53, BAX, TIMP-2).
  • In vivo studies demonstrated that PER1 knockdown enhanced tumor weight and volume in mice.

Conclusions:

  • PER1 functions as a tumor suppressor gene in oral squamous cell carcinoma.
  • PER1 plays a critical role in regulating cancer cell proliferation, apoptosis, and metastasis.
  • Targeting PER1 may represent a promising therapeutic strategy for oral cancer treatment.
Keywords:
PER1circadian clockoral cancertumortumor-related genes

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