PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4-p-STAT3-MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma

Cisplatin is a widely used platinum-based chemotherapeutic agent for hypopharyngeal squamous cell carcinoma (HSCC). However, resistance to cisplatin limits its use for the treatment of HSCC, and the underlying molecular mechanism requires further investigation. The present study performed functional assays to determine whether the expression of plant homeodomain finger protein 20 (PHF20) may be involved in the apoptosis and cisplatin resistance of HSCC. The expression levels of PHF20 were higher in cisplatin-resistant HSCC cells compared with those in cisplatin-sensitive cells. The inhibition of PHF20 suppressed cell viability but did not affect the migratory and invasive abilities of HSCC cells compared with those of negative control-transfected cells. Furthermore, PHF20 inhibition reduced cell viability by enhancing apoptosis compared with those in the control cells in vitro. Notably, the inhibition of PHF20 sensitized HSCC cells to cisplatin, thus increasing apoptosis via the signal transducer and activator of transcription 3 (STAT3)-myeloid cell leukemia-1 (MCL1) pathway. Octamer-binding transcription factor 4 (OCT4) overexpression restored phosphorylated STAT3-MCL1-mediated apoptosis induced by PHF20 inhibition. In vivo experiments confirmed that PHF20 silencing induced tumor growth and increased apoptosis in HSCC cells compared with those in the control cells. Thus, PHF20 inhibition may promote apoptosis and improve cisplatin chemosensitivity via the OCT4-p-STAT3-MCL1 signaling pathway in HSCC.