Deng Haiyan, Zhang Juan, Chen Shuaijun, Liang Tingfeng, Hu Xueyong, Li Jing, He Yong, Yu Feng, Yu Chaosheng
Department of Otorhinolaryngology-Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, China.
Department of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Curr Med Chem. 2025 Jun 25. doi: 10.2174/0109298673378818250610053439.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with a poor prognosis. Ubiquitination is a complex post translational modification involved in cancer progression. However, ubiquitination related genes (URGs) in immunotherapy of NPC remains largely unexplored.
Differentially expressed URGs were screened based on the single-cell RNA sequencing (scRNA-seq) dataset and a risk model of NPC was constructed and evaluated for prognostic significance. The oncogenic role of RNF149 in NPC was investigated through in vitro and in vivo experiments, including tumor cells, NPC-like organoids, and tumor-bearing mice.
scRNA-seq data showed that URGs scores were higher in cancer cells than in normal epithelial cells. We identified 216 differentially expressed URGs between cancer and normal epithelial cells, but only 33 differentially expressed URGs associated with prognosis. Based on 33 URGs, TCGA-HNSC samples were classified into two distinct subtypes with significant differences in the tumor immune microenvironment, immunotherapy effect, and survival-prognostic genes. Using LASSO algorithm, 13 URGs were selected to construct a risk model, which demonstrated high predictive performance. The expression profiles of these 13 URGs were analyzed in TCGA-HNSC tumor and adjacent non-cancerous samples, and six URGs (BSPRY, OTUB1, PJA1, RNF149, RNF181, USP10) exhibited consistent expression trends. Moreover, quantitative real-- time PCR revealed that RNF149 was up-regulated expression in NPC cell compared to the NP69 cells. RNF149 knockdown significantly impeded the proliferative, migratory, and invasive capabilities and exaggerated apoptosis of NPC cells. RNF149 knockdown cells exhibited a reduced capacity to form NPC organoids in a 3D culture system. shRNA- RNF149 diminished subcutaneous tumorigenic capacity of HK-1 cells compared to the control group.
The URGs-based prognostic risk model offers a robust tool for predicting immunotherapy efficacy in NPC and RNF9 promotes NPC progression.
A URGs-related prognostic risk model capable of predicting clinical outcomes in NPC patients and RNF9 promotes NPC progression. Our findings are expected to provide new strategies to improve outcomes for NPC patients.
鼻咽癌（NPC）是一种侵袭性恶性肿瘤，预后较差。泛素化是一种参与癌症进展的复杂翻译后修饰。然而，泛素化相关基因（URGs）在鼻咽癌免疫治疗中的作用仍 largely 未被探索。
基于单细胞 RNA 测序（scRNA-seq）数据集筛选差异表达的 URGs，并构建鼻咽癌风险模型并评估其预后意义。通过体外和体内实验，包括肿瘤细胞、鼻咽癌样类器官和荷瘤小鼠，研究 RNF149 在鼻咽癌中的致癌作用。
scRNA-seq 数据显示癌细胞中的 URGs 评分高于正常上皮细胞。我们鉴定出癌症与正常上皮细胞之间有 216 个差异表达的 URGs，但只有 33 个差异表达的 URGs 与预后相关。基于 33 个 URGs，TCGA-HNSC 样本被分为两个不同亚型，在肿瘤免疫微环境、免疫治疗效果和生存预后基因方面存在显著差异。使用 LASSO 算法，选择 13 个 URGs 构建风险模型，该模型显示出高预测性能。在 TCGA-HNSC 肿瘤和相邻非癌样本中分析了这 13 个 URGs 的表达谱，6 个 URGs（BSPRY、OTUB1、PJA1、RNF149、RNF181、USP10）表现出一致的表达趋势。此外，定量实时 PCR 显示与 NP69 细胞相比，RNF149 在鼻咽癌细胞中表达上调。RNF149 敲低显著阻碍了鼻咽癌细胞的增殖、迁移和侵袭能力，并加剧了细胞凋亡。RNF149 敲低细胞在三维培养系统中形成鼻咽癌类器官的能力降低。与对照组相比，shRNA-RNF149 降低了 HK-1 细胞的皮下致瘤能力。
基于 URGs 的预后风险模型为预测鼻咽癌免疫治疗疗效提供了一个强大的工具，且 RNF9 促进鼻咽癌进展。
一个能够预测鼻咽癌患者临床结局的 URGs 相关预后风险模型，且 RNF9 促进鼻咽癌进展。我们的研究结果有望为改善鼻咽癌患者的预后提供新策略。
