You Yuanhe, Du Zhong, Tian Zhuowei, Yu Fan, Li Shunshun, He Jie, Xiao Meng, Wang Yanan
Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Oral Dis. 2025 Jun;31(6):1692-1703. doi: 10.1111/odi.15263. Epub 2025 Jan 21.
This study aimed to investigate potential cellular senescence inhibitory genes (CSIGs) and discover novel therapeutic targets in head and neck squamous cell carcinoma.
Dysregulated CSIGs were identified based on The Cancer Genome Atlas (TCGA) and the Human Aging Genomic Resources (HAGR) database. Prognostic value and immune infiltration were assessed through bioinformatic analysis. Cell proliferation was evaluated using CCK-8, Edu assay, and colony formation assays in vitro. Western blotting and real-time PCR were used to evaluate LIMA1 expression. Clinical validation of LIMA1 expression was performed in our validated cohort.
In this study, differential analysis and functional enrichment analysis identified 26 differentially expressed senescence inhibitory genes. Among them, LIMA1 was found to be an independent prognostic marker and associated immune infiltration. Knockdown of LIMA1 inhibited HNSCC cell growth and increased the expression of senescence markers. Further experiments revealed that LIMA1 expression was partially regulated by the IL6/STAT3 signaling pathway. Immunohistochemistry further validated the clinical significance of LIMA1 expression and its association with IL6 and CD8 T cells in our hospital's HNSCC tissues.
LIMA1 is a prognostic senescence-inhibitory gene in HNSCC. The IL6/STAT3/LIMA1 axis represents a novel molecular mechanism underlying cellular senescence resistance in HNSCC.
本研究旨在探究潜在的细胞衰老抑制基因（CSIGs），并在头颈部鳞状细胞癌中发现新的治疗靶点。
基于癌症基因组图谱（TCGA）和人类衰老基因组资源（HAGR）数据库鉴定失调的CSIGs。通过生物信息学分析评估预后价值和免疫浸润情况。在体外使用CCK-8、Edu检测和集落形成检测评估细胞增殖。采用蛋白质免疫印迹法和实时定量PCR评估LIMA1表达。在我们的验证队列中对LIMA1表达进行临床验证。
在本研究中，差异分析和功能富集分析鉴定出26个差异表达的衰老抑制基因。其中，LIMA1被发现是一个独立的预后标志物且与免疫浸润相关。敲低LIMA1可抑制头颈部鳞状细胞癌细胞生长并增加衰老标志物的表达。进一步实验表明，LIMA1表达部分受IL6/STAT3信号通路调控。免疫组织化学进一步验证了LIMA1表达在我院头颈部鳞状细胞癌组织中的临床意义及其与IL6和CD8 T细胞的关联。
LIMA1是头颈部鳞状细胞癌中的一个预后衰老抑制基因。IL6/STAT3/LIMA1轴代表了头颈部鳞状细胞癌中细胞衰老抗性的一种新分子机制。
