The present findings suggest that necdin and Bmi1 use their downstream cell-cycle regulatory systems via Cdk1 and p16 pathways to control NPC proliferation: Necdin suppresses Cdk1 expression (independently of Bmi1), increases p16 expression by repressing Bmi1, and suppresses NPC proliferation, whereas Bmi1 suppresses p16 expression (independently of necdin), increases Cdk1 expression by repressing necdin, and increases NPC proliferation. Here, CDKN2A is linked to nasopharyngeal carcinoma.