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

Abstract

Recent findings on the existence of oncogenic fusion genes in a wide array of solid tumors, including head and neck squamous cell carcinoma (HNSCC), suggests that fusion genes have become attractive targets for cancer diagnosis and treatment. In this study, we showed for the first time that a read-through fusion gene JMJD7-PLA2G4B is presented in HNSCC, splicing neighboring jumonji domain containing 7 (JMJD7) and phospholipase A2, group IVB (PLA2G4B) genes together. Ablation of JMJD7-PLA2G4B significantly inhibited proliferation of HNSCC cells by promoting G1 cell cycle arrest and increased starvation-induced cell death compared to JMJD7-only knockdown HNSCC cells. Mechanistically, we found that JMJD7-PLA2G4B modulates phosphorylation of Protein Kinase B (AKT) to promote HNSCC cell survival. Moreover, JMJD7-PLA2G4B also regulated an E3 ligase S-phase kinase-associated protein 2 (SKP2) to control the cell cycle progression from G1 phase to S phase by inhibiting Cyclin-dependent kinase inhibitor 1 (p21) and 1B (p27) expression. Our study provides novel insights into the oncogenic control of JMJD7-PLA2G4B in HNSCC cell proliferation and survival, and suggests that JMJD7-PLA2G4B may serve as an important therapeutic target and prognostic marker for HNSCC development and progression.

• Authors: Yingduan Cheng, Yi Wang, Jiong Li, Insoon Chang, Cun-Yu Wang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 2 Pg. 1972-1982 (Jan 10 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28030848 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Oncogene Proteins, Fusion
• Jumonji Domain-Containing Histone Demethylases
• Oncogene Protein v-akt
• Group IV Phospholipases A2
• PLA2G4B protein, human

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Squamous Cell (diagnosis, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Group IV Phospholipases A2 (genetics, physiology)
• HCT116 Cells
• HEK293 Cells
• HT29 Cells
• Head and Neck Neoplasms (diagnosis, genetics, pathology)
• Humans
• Jumonji Domain-Containing Histone Demethylases (genetics, physiology)
• MCF-7 Cells
• Oncogene Protein v-akt (metabolism)
• Oncogene Proteins, Fusion (genetics, physiology)
• Phosphorylation
• Squamous Cell Carcinoma of Head and Neck