A novel read-through transcript JMJD7-PLA2G4B regulates head and neck squamous cell carcinoma cell proliferation and...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Oncogenic fusion genes are increasingly recognized as key drivers in various solid tumors.
• Head and neck squamous cell carcinoma (HNSCC) presents a complex landscape where fusion genes are emerging as diagnostic and therapeutic targets.

Purpose of the Study:

• To identify and characterize novel oncogenic fusion genes in HNSCC.
• To investigate the functional role of the identified fusion gene in HNSCC proliferation and survival.
• To elucidate the molecular mechanisms underlying the oncogenic activity of JMJD7-PLA2G4B.

Main Methods:

• Fusion gene identification using next-generation sequencing.
• Functional studies involving gene ablation (e.g., CRISPR-Cas9) in HNSCC cell lines.
• Cell cycle analysis (e.g., flow cytometry) and apoptosis assays.
• Western blotting to assess protein phosphorylation and expression levels (e.g., AKT, SKP2, p21, p27).

Main Results:

• Discovery of the novel read-through fusion gene JMJD7-PLA2G4B in HNSCC.
• Ablation of JMJD7-PLA2G4B significantly inhibited HNSCC cell proliferation via G1 cell cycle arrest and enhanced starvation-induced cell death.
• JMJD7-PLA2G4B promotes HNSCC survival by modulating AKT phosphorylation and regulating SKP2 to control cell cycle progression through p21 and p27 inhibition.

Conclusions:

• JMJD7-PLA2G4B is an oncogenic fusion gene driving HNSCC proliferation and survival.
• The fusion gene acts through the AKT signaling pathway and regulates E3 ligase SKP2.
• JMJD7-PLA2G4B represents a promising therapeutic target and prognostic biomarker for HNSCC.