DIAPH1 Is Upregulated and Inhibits Cell Apoptosis through ATR/p53/Caspase-3 Signaling Pathway in Laryngeal Squamous...

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Cancer bioinformatics identifies key genes and pathways in tumorigenesis.
• Diaphanous related formin 1 (DIAPH1) expression correlates with poor survival in head and neck cancers, including laryngeal squamous cell carcinoma (LSCC).
• The specific role of DIAPH1 in LSCC remains largely uncharacterized.

Purpose of the Study:

• To investigate the expression, function, and molecular mechanisms of DIAPH1 in LSCC.
• To determine if DIAPH1 acts as an oncogene in LSCC.
• To elucidate the signaling pathway involved in DIAPH1-mediated apoptosis regulation.

Main Methods:

• Bioinformatics analysis to identify DIAPH1 as a potential key gene.
• Immunohistochemistry and Western blot to assess DIAPH1 protein levels in LSCC tissues.
• RNA interference (RNAi) to create DIAPH1-knockdown LSCC cell lines (AMC-HN-8, FD-LSC-1).
• Flow cytometry to evaluate apoptosis.
• Western blot to analyze key proteins in apoptosis and DNA damage pathways (ATR, p53, Bax, Caspase-3, -8, -9).

Main Results:

• DIAPH1 was significantly upregulated in LSCC tissues and cell lines.
• DIAPH1 knockdown led to increased apoptosis in LSCC cells.
• DIAPH1 knockdown resulted in elevated protein levels of ATR, phosphorylated p53 (p-p53), Bax, and cleaved Caspase-3, -8, and -9.
• These findings suggest DIAPH1 inhibits apoptosis.

Conclusions:

• DIAPH1 is upregulated in LSCC and functions as an oncogene.
• DIAPH1 promotes LSCC progression by inhibiting apoptosis.
• The anti-apoptotic effect of DIAPH1 in LSCC involves the ATR/p53/caspase-3 signaling pathway.