Wang Xueying, Wang Junrong, Wang Lei, Song Ming, Meng Hongxue, Guo Erliang, Miao Susheng
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central, South University, Changsha, Hunan, China.
Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China.
J Cell Mol Med. 2025 Feb;29(3):e70364. doi: 10.1111/jcmm.70364.
Cathepsin L (CTSL) is an important oncogene. However, its mechanism of action in laryngeal cancer is still unclear. This study aims to explore the role of CTSL in laryngeal cancer and its clinical significance. Conducting bioinformatics analysis utilising the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Performing CCK8 analysis, Western blotting, qRT-PCR, wound healing assay and transwell invasion assay. Additionally, conducting immunoprecipitation experiments and immunohistochemical staining to investigate the impact of CTSL on cell proliferation, autophagy and related signalling pathways. We observed a significant upregulation of CTSL in laryngeal cancer tissues, and its elevated levels are indicative of poor prognosis in laryngeal cancer patients. The proliferation of laryngeal cancer cells relies on the expression of CTSL, with overexpression of this gene enhancing the proliferative capacity of these cells. Concurrently, CTSL is closely associated with the autophagic levels in laryngeal cancer cells. During the autophagic process mediated by CTSL, the IL6-JAK-STAT3 signalling pathway is activated, suggesting that CTSL promotes autophagy through the IL6-JAK-STAT3 pathway. Considering the correlation between CTSL and autophagy, we developed and validated a multi-gene signature. The risk score derived from this signature demonstrates significant potential in predicting various aspects. We found that CTSL upregulates autophagy in laryngeal cancer cells by activating the IL6-JAK-STAT3 signalling pathway. By taking into account the autophagy-regulating role of CTSL, the clinical predictive ability of CTSL in HNSC can be enhanced.
组织蛋白酶L（CTSL）是一种重要的癌基因。然而，其在喉癌中的作用机制仍不清楚。本研究旨在探讨CTSL在喉癌中的作用及其临床意义。利用癌症基因组图谱（TCGA）数据库和基因表达综合数据库（GEO）进行生物信息学分析。进行CCK8分析、蛋白质免疫印迹法、定量逆转录聚合酶链反应、伤口愈合试验和Transwell侵袭试验。此外，进行免疫沉淀实验和免疫组织化学染色，以研究CTSL对细胞增殖、自噬及相关信号通路的影响。我们观察到喉癌组织中CTSL显著上调，其水平升高表明喉癌患者预后不良。喉癌细胞的增殖依赖于CTSL的表达，该基因的过表达增强了这些细胞的增殖能力。同时，CTSL与喉癌细胞中的自噬水平密切相关。在CTSL介导的自噬过程中，IL6-JAK-STAT3信号通路被激活，这表明CTSL通过IL6-JAK-STAT3通路促进自噬。考虑到CTSL与自噬之间的相关性，我们开发并验证了一个多基因特征。从该特征得出的风险评分在预测各个方面具有显著潜力。我们发现CTSL通过激活IL6-JAK-STAT3信号通路上调喉癌细胞中的自噬。通过考虑CTSL的自噬调节作用，可以增强CTSL在头颈部鳞状细胞癌中的临床预测能力。
