Yang Ming, Ke Zhaoyang, Wang Daji
Department of Otorhinolaryngology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, China.
Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
Open Life Sci. 2024 Oct 30;19(1):20220975. doi: 10.1515/biol-2022-0975. eCollection 2024.
The resistance of tumor cells to chemotherapy drugs is a critical determinant in the recurrence and metastasis of nasopharyngeal carcinoma (NPC). Therefore, it is crucial to identify effective biotargets that can enhance the sensitivity of NPC cells to chemotherapy drugs. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) plays a central role in regulating chemotherapy resistance across various tumor types. However, its specific function in NPC cells remains unclear. This study reveals that hnRNPK is overexpressed in NPC tissues while weakly expressed in normal nasopharyngeal tissues. The expression level of hnRNPK is negatively associated with NPC patient survival. Importantly, hnRNPK is a key inducer of chemotherapy resistance in NPC, as evidenced by the significant increase in NPC cell sensitivity to cisplatin following hnRNPK knockdown. Mechanistically, hnRNPK induces chemotherapy resistance in NPC cells by suppressing the activation of the Akt/caspase 3 pathway. In NPC tumor-bearing mice, hnRNPK knockdown enhances the efficacy of cisplatin chemotherapy. Consequently, this work identifies a potential target for enhancing the sensitivity of NPC cells to chemotherapy.
肿瘤细胞对化疗药物的耐药性是鼻咽癌(NPC)复发和转移的关键决定因素。因此,识别能够增强NPC细胞对化疗药物敏感性的有效生物靶点至关重要。异质性核糖核蛋白K(hnRNPK)在调节多种肿瘤类型的化疗耐药性中起核心作用。然而,其在NPC细胞中的具体功能仍不清楚。本研究表明,hnRNPK在NPC组织中高表达,而在正常鼻咽组织中弱表达。hnRNPK的表达水平与NPC患者的生存率呈负相关。重要的是,hnRNPK是NPC化疗耐药的关键诱导因子,hnRNPK敲低后NPC细胞对顺铂的敏感性显著增加证明了这一点。机制上,hnRNPK通过抑制Akt/半胱天冬酶3途径的激活诱导NPC细胞产生化疗耐药性。在荷NPC肿瘤的小鼠中,hnRNPK敲低增强了顺铂化疗的疗效。因此,这项工作确定了一个增强NPC细胞对化疗敏感性的潜在靶点。