Jia Yue, Liu Jiaojiao, Shi Junqi, Zhang Chunming, Wang Xinfang, Zhao Liting, Lou Yichen, Guan Xiaoya, Huangfu Hui
Department of Otolaryngology Head & Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Oncol Rep. 2025 Feb;53(2). doi: 10.3892/or.2024.8861. Epub 2025 Jan 3.
Laryngeal squamous cell carcinoma (LSCC), which represents a significant proportion of head and neck squamous cell carcinoma cases, is often diagnosed at advanced stages, underscoring the urgent need for effective biomarkers and therapeutic targets. Junctional adhesion molecule 3 () is implicated in various types of cancer; however, its role in LSCC remains unclear. Therefore, the present study aimed to investigate the epigenetic regulation and tumor‑suppressive functions and mechanisms of in LSCC. Bioinformatics analysis and 5‑Aza‑2'‑deoxycytidine treatment, which restored expression as confirmed by reverse transcription‑quantitative PCR and western blotting, revealed that aberrant hypermethylation of the promoter was associated with reduced expression and poorer clinical outcomes in patients with LSCC. experiments, including Cell Counting Kit 8, colony formation and Transwell assays, demonstrated that overexpression inhibited LSCC cell proliferation, migration and invasion. Western blotting and immunofluorescence analysis revealed that the tumor‑suppressive function of JAM3 was mediated through activation of the Hippo pathway. By contrast, both and experiments showed that knockdown enhanced these oncogenic behaviors by inhibiting the Hippo pathway, suggesting its critical tumor‑suppressive role. In conclusion, the results of the present study indicated that may be epigenetically downregulated and could function as a novel tumor suppressor gene through the Hippo pathway in LSCC, offering insights into developing targeted treatments and diagnostics.
喉鳞状细胞癌（LSCC）在头颈部鳞状细胞癌病例中占相当大的比例，通常在晚期才被诊断出来，这凸显了对有效生物标志物和治疗靶点的迫切需求。连接粘附分子3（JAM3）与多种类型的癌症有关；然而，其在LSCC中的作用仍不清楚。因此，本研究旨在探讨JAM3在LSCC中的表观遗传调控、肿瘤抑制功能及机制。生物信息学分析和5-氮杂-2'-脱氧胞苷处理（逆转录定量PCR和蛋白质免疫印迹法证实其恢复了JAM3表达）显示，JAM3启动子的异常高甲基化与LSCC患者JAM3表达降低及较差的临床结果相关。细胞计数试剂盒8、集落形成和Transwell实验等实验表明，JAM3过表达抑制了LSCC细胞的增殖、迁移和侵袭。蛋白质免疫印迹法和免疫荧光分析显示，JAM3的肿瘤抑制功能是通过激活Hippo通路介导的。相比之下，RNA干扰和基因敲除实验均表明，JAM3敲低通过抑制Hippo通路增强了这些致癌行为，表明其具有关键的肿瘤抑制作用。总之，本研究结果表明，JAM3可能在表观遗传上被下调，并可能通过Hippo通路在LSCC中作为一种新型肿瘤抑制基因发挥作用，为开发靶向治疗和诊断方法提供了思路。
