Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) utilizes immunosuppressive phenotypes to evade immune detection, facilitating tumor initiation and progression.
• DNA damage repair mechanisms are closely linked to tumor cell immunophenotype modulation.
• The role of flap endonuclease-1 (FEN1), a key enzyme in DNA repair, in tumor immunity remains largely unexplored.

Purpose of the Study:

• To investigate the correlation between FEN1 expression and the tumor immune microenvironment in OSCC.
• To determine the effect of FEN1 downregulation on OSCC growth and biological behaviors.
• To elucidate the molecular mechanisms by which FEN1 influences immunosuppressive phenotypes in OSCC.

Main Methods:

• Clinicopathological analysis of FEN1 expression in OSCC.
• In vitro studies involving FEN1 knockdown in OSCC cells.
• Multiplex immunohistochemistry (mIHC) to assess FEN1 and immunosuppressive markers.
• Analysis of the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway.

Main Results:

• FEN1 was found to be overexpressed in OSCC, correlating with an inhibitory immune microenvironment.
• Downregulation of FEN1 significantly inhibited OSCC tumor growth and suppressed malignant biological behaviors.
• FEN1 expression was directly correlated with the acquisition of immunosuppressive phenotypes, including human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1).
• FEN1 was identified as a regulator of HLA-DR and PD-L1 expression via the IFN-γ/JAK/STAT1 signaling pathway.

Conclusions:

• FEN1 plays a critical role in promoting OSCC immune evasion and tumor progression.
• Targeting FEN1 offers a novel therapeutic strategy for OSCC immunotherapy.
• FEN1 represents a potential biomarker for predicting immune evasion and a therapeutic target in oral cancer.