长链非编码RNA SNHG14通过与U2AF2结合上调Notch2促进鼻咽癌顺铂耐药
LncRNA SNHG14 Facilitates Cisplatin Resistance Through Upregulating Notch2 via Binding to U2AF2 in Nasopharyngeal Carcinoma.
作者信息
Yan Sijia, Zhang Puhua, Tan Shuai, Mo Haiyun, Yang Yanlin
机构信息
Oncology Department, Affiliated Nanhua Hospital of University of South China, Hunan, China.
出版信息
Head Neck. 2025 Apr;47(4):1125-1134. doi: 10.1002/hed.28016. Epub 2024 Nov 27.
BACKGROUND
Cisplatin (DDP) is one of the commonly used chemotherapeutic drugs for nasopharyngeal carcinoma (NPC) patients, and the resistance of tumor cells to cisplatin is main obstacle for NPC treatment. This study explored effect and possible mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) on drug resistance of NPC cells to cisplatin.
METHODS
Levels of SNHG14 and Notch2 in NPC tissues and cells were confirmed using RT-qPCR. Western blot detected Notch2 and ABCB1 expression in NPC cells. IC50 of cisplatin-treated NPC cells was tested utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell proliferation and apoptosis were evaluated utilizing colony formation experiment and flow cytometry, respectively. RNA immunoprecipitation (RIP) assay was utilized to validate the target genes of U2AF2. Notch2 mRNA stability was tested using actinomycin D.
RESULTS
SNHG14 level was increased in both cisplatin-resistant NPC tissues and cell lines. SNHG14 silencing in HNE1/DDP cells resulted in inhibition of chemoresistance to cisplatin. Conversely, upregulation of SNHG14 in HNE1 cells enhanced their resistance to cisplatin. SNHG14 exhibited an interaction with U2AF2, leading to stabilization of Notch2 mRNA. Finally, Notch2 was involved in SNHG14-mediated cisplatin resistance in NPC cells.
CONCLUSION
Our findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.
背景
顺铂(DDP)是鼻咽癌(NPC)患者常用的化疗药物之一,肿瘤细胞对顺铂的耐药性是鼻咽癌治疗的主要障碍。本研究探讨了长链非编码RNA小核仁RNA宿主基因14(SNHG14)对NPC细胞顺铂耐药性的影响及可能机制。
方法
采用RT-qPCR检测NPC组织和细胞中SNHG14和Notch2的水平。Western blot检测NPC细胞中Notch2和ABCB1的表达。利用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)检测顺铂处理的NPC细胞的半数抑制浓度(IC50)。分别采用集落形成实验和流式细胞术评估细胞增殖和凋亡。采用RNA免疫沉淀(RIP)实验验证U2AF2的靶基因。用放线菌素D检测Notch2 mRNA的稳定性。
结果
顺铂耐药的NPC组织和细胞系中SNHG14水平均升高。HNE1/DDP细胞中SNHG14沉默导致对顺铂化疗耐药性的抑制。相反,HNE1细胞中SNHG14的上调增强了它们对顺铂的耐药性。SNHG14与U2AF2存在相互作用,导致Notch2 mRNA的稳定。最后,Notch2参与了SNHG14介导的NPC细胞顺铂耐药。
结论
我们的研究结果表明,SNHG14通过U2AF2/Notch2轴在促进NPC细胞对顺铂的化疗耐药中起重要作用。这些结果突出了鼻咽癌治疗的潜在靶点。