Fig. 3

Key oncogenic mechanisms in HPV-negative and HPV-positive laryngeal cancers. A: Smoking and alcohol consumption cause mutations in the TP53 gene and affect DNA methyltransferase (DNMT)-dependent regulation of miRNA expression, leading to tumor transformation. B: By engaging the ubiquitin-protein ligase E3A (E6AP), E6 binds with p53 and promotes its degradation. Ubiquitinated TP53 also causes changes in the expression of miR-16, miR-15a, miR-143, miR-145, and miR-195. Cell cycle protein D1 expression begins when cell growth signaling occurs. Cell cycle protein E then activates CDK2, phosphorylates RB, releases E2F, and initiates cell cycle entry gene transcription