An Ran, Xu Xiaolin, Wang Yue, Ding Jiayi, Li Boyu, Yang Fan, Liu Ming, Tian Linli
Department of Otorhinolaryngology, Head and Neck Surgery, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150086, Heilongjiang, China.
Sci Rep. 2025 Apr 23;15(1):14011. doi: 10.1038/s41598-025-98989-8.
Cell cycle protein E2 (CCNE2) is a member of the Cyclin family, known for driving tumor cell proliferation and invasion. However, the mechanism of its action in head and neck squamous cell carcinoma (HNSCC) remains unclear. The aim of this study is to investigate the relationship between CCNE2 and cisplatin resistance and survival prognosis of head and neck squamous cell carcinoma. We performed transcriptomic sequencing of HNSCC and HNSCC/DDP. Kaplan-Meier analysis and COX regression analysis were used to evaluate the relationship between CCNE2 expression and survival prognosis of HNSCC patients. Multiple potential biological functions of CCNE2 in HNSCC were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Single-sample gene set enrichment analysis (ssGSEA) was used to explore tumor immune infiltration. The potential mechanism of CCNE2 was explored by molecular docking and immunoprecipitation. Cell migration, cell invasion and cell proliferation assays were used to investigate the mechanism of CCNE2 in HNSCC. CCNE2 is up-regulated in HNSCC tissues and cell lines and is associated with poor prognosis. The high expression of CCNE2 in HNSCC is associated with clinical significance. GO and KEGG analysis showed that ccne2 related genes may be involved in the regulation of DNA double-strand break repair and DNA metabolic process. CCNE2 expression was positively correlated with the infiltration levels of helper T cells, Tcm cells and Th2 cells, and negatively correlated with the infiltration levels of DC, neutrophils and pDC. CCNE2 regulates the invasion, migration and proliferation of HNSCC cells by targeting MNAT1. CCNE2 also altered cisplatin resistance in HNSCC/DDP. CCNE2 may be an independent prognostic biomarker of HNSCC through MNAT1, which provides new ideas for cisplatin resistance and therapeutic targets of HNSCC.
细胞周期蛋白E2（CCNE2）是细胞周期蛋白家族的成员，以驱动肿瘤细胞增殖和侵袭而闻名。然而，其在头颈部鳞状细胞癌（HNSCC）中的作用机制仍不清楚。本研究的目的是探讨CCNE2与头颈部鳞状细胞癌顺铂耐药性及生存预后之间的关系。我们对HNSCC和HNSCC/DDP进行了转录组测序。采用Kaplan-Meier分析和COX回归分析来评估CCNE2表达与HNSCC患者生存预后之间的关系。利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）确定了CCNE2在HNSCC中的多种潜在生物学功能。采用单样本基因集富集分析（ssGSEA）来探索肿瘤免疫浸润。通过分子对接和免疫沉淀探索了CCNE2的潜在机制。采用细胞迁移、细胞侵袭和细胞增殖实验来研究CCNE2在HNSCC中的作用机制。CCNE2在HNSCC组织和细胞系中上调，与预后不良相关。CCNE2在HNSCC中的高表达具有临床意义。GO和KEGG分析表明，ccne2相关基因可能参与DNA双链断裂修复和DNA代谢过程的调控。CCNE2表达与辅助性T细胞、中央记忆T细胞和Th2细胞的浸润水平呈正相关，与树突状细胞、中性粒细胞和浆细胞样树突状细胞的浸润水平呈负相关。CCNE2通过靶向MNAT1调节HNSCC细胞的侵袭、迁移和增殖。CCNE2还改变了HNSCC/DDP中的顺铂耐药性。CCNE2可能通过MNAT1成为HNSCC的独立预后生物标志物，这为HNSCC的顺铂耐药性和治疗靶点提供了新的思路。
