These results reveal a novel mechanism by which miR-296-3p negatively regulated by nicotine directly targets MK2-induced Ras/Braf/Erk/Mek/c-Myc or PI3K/AKT/c-Myc signaling to stimulate its own expression and suppress NPC cell proliferation and metastasis. miR-296-3p may thus serve as a therapeutic target to reverse chemotherapy resistance of NPC.
Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy.
This study suggests that PI3K p110α overexpression, which is attributed, at least in part, to PIK3CA gene amplification, may contribute to NPC pathogenesis.
Our studies are the first to demonstrate that reduced CTGF as an unfavorable prognosis factor mediates the activation of miR-18b, an oncomir directly suppresses CTGF expression, by PI3K/AKT/C-Jun and C-Myc and promotes cell growth of NPC.
These findings show that mutated PI3K may be involved in the NPC tumorigenesis but does not affect patient's prognosis, suggesting that PI3K is a potential target in NPC for targeted therapeutics using specific kinase inhibitors.
Taken together, BMI-1 depletion enhanced the chemosensitivity of NPC cells by inducing apoptosis; which is associated with inhibition of the PI3K/AKT pathway.