PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4-p-STAT3-MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma
PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4-p-STAT3-MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma
复制标题
PHF20抑制通过OCT4-p-STAT3-MCL1信号通路促进下咽鳞状细胞癌细胞凋亡和顺铂化疗敏感性
DOI：
10.3892/ijo.2021.5218
复制
发表时间：
2021-07-01
影响因子：
5.2
通讯作者：
Xu, Wei
中科院分区：
文献类型：
--
作者：
Liu, Xiuxiu;Zhang, Zhancheng;Xu, Wei
顺铂是一种广泛应用于下咽鳞状细胞癌（HSCC）的铂类化疗药物。然而，顺铂的耐药性限制了其在HSCC治疗中的应用，其潜在的分子机制需要进一步研究。本研究通过功能分析来确定植物同源域指蛋白20（PHF 20）的表达是否可能参与HSCC的凋亡和顺铂耐药。PHF 20在顺铂耐药细胞中的表达水平高于顺铂敏感细胞。与阴性对照转染细胞相比，PHF 20的抑制了细胞活力，但不影响HSCC细胞的迁移和侵袭能力。此外，PHF 20抑制通过增强细胞凋亡而降低细胞活力。值得注意的是，PHF 20的抑制使HSCC细胞对顺铂敏感，从而通过信号转导子和转录激活子3（STAT 3）-骨髓细胞白血病-1（MCL 1）途径增加凋亡。八聚体结合转录因子4（OCT 4）过表达恢复了磷酸化STAT 3-MCL 1介导的PHF 20抑制诱导的细胞凋亡。体内实验证实，与对照细胞相比，PHF 20沉默诱导HSCC细胞的肿瘤生长和凋亡增加。因此，PHF 20抑制可能通过HSCC中的OCT 4-p-STAT 3-MCL 1信号通路促进细胞凋亡并改善顺铂化疗敏感性。
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.