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The Molecular Landscape and Biological Alterations Induced by PRAS40-Knockout in Head and Neck Squamous Cell

Gang Chen1, Zhexuan Li1, Changhan Chen1

  • 1Department of Otolaryngology-Head and Neck Surgery, The Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Oncology
|January 25, 2021
PubMed

Insights

High Prolin-rich Akt substrate of 40 kDa (PRAS40) mRNA expression is a favorable prognostic factor in head and neck squamous cell carcinoma (HNSCC). PRAS40 suppression promotes HNSCC cell growth and invasion, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Prolin-rich Akt substrate of 40 kDa (PRAS40) links PI3K/Akt and mTORC1 pathways, crucial in disease development.
  • The role of PRAS40 in head and neck squamous cell carcinoma (HNSCC) is not well understood.

Purpose of the Study:

  • To investigate the prognostic value of PRAS40 in HNSCC.
  • To elucidate the molecular mechanisms underlying PRAS40's function in HNSCC.
  • To explore the relationship between PRAS40 and tumor-infiltrating immune cells in HNSCC.

Main Methods:

  • Analysis of clinical and mRNA data from 498 HNSCC patients.
  • CRISPR/Cas9-mediated PRAS40 knockout in HNSCC cell lines.
  • RNA-sequencing to identify differentially expressed genes post-PRAS40 knockout.
  • Quantitative PCR (qPCR) and Western blotting for molecular validation.
  • Analysis of tumor-infiltrating immune cells (CD8+ T, T follicular helper, Th17 cells).

Main Results:

  • High PRAS40 mRNA expression correlated with a favorable prognosis in HNSCC patients.
  • PRAS40 knockout enhanced colony formation, migration, and invasion of HNSCC cells.
  • PRAS40 knockout led to differential expression of genes enriched in TGF-beta, PI3K-Akt, P53, mTOR, and NF-κB signaling pathways.
  • High PRAS40 expression was associated with increased CD8+ T and T follicular helper cells, and decreased Th17 cells in HNSCC tumors.

Conclusions:

  • PRAS40 acts as a suppressor in HNSCC, with high expression being a favorable prognostic indicator.
  • Altered molecular pathways and tumor-infiltrating immune cell profiles suggest PRAS40's role in HNSCC progression.
  • PRAS40 represents a potential prognostic predictor and therapeutic target for HNSCC.
Keywords:
CRISPR/Cas9The Cancer Genome Atlashead and neck squamous cell carcinomaimmunomicro-environmentmetastasisprolin-rich Akt substrate of 40 kDa

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