Shimojukkoku Yudai, Nguyen Phuong Thao, Ishihata Kiyohide, Ishida Takayuki, Kajiya Yuka, Oku Yasunobu, Kawaguchi Koshiro, Tsuchiyama Takahiro, Saijo Hideto, Shima Kaori, Sasahira Tomonori
Department of Molecular Oral Pathology and Oncology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan.
Department of Oral and Maxillofacial Surgery, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Discov Oncol. 2024 Nov 26;15(1):714. doi: 10.1007/s12672-024-01611-y.
Oral squamous cell carcinoma (OSCC) exhibits pronounced local invasiveness and a propensity for lymph node metastasis. Given its frequent detection at advanced stages and the consequential postoperative functional impairments, the identification of effective molecular markers for early detection and treatment is imperative. Early growth response-1 (EGR-1) serves as a versatile transcription factor expressed across various cell types. Its role in cancer is contentious, acting as either an oncogene or a tumor suppressor gene.
This study undertook comprehensive analyses, including big data scrutiny, expression profiling using 50 OSCC samples, and in vitro functional assessments, to elucidate EGR-1's involvement in OSCC.
Comparative analysis revealed significantly reduced EGR-1 expression in oral cancer tissues compared to healthy controls or normal oral mucosa. In vitro experimentation with multiple OSCC cell lines demonstrated that EGR-1 curbed cell proliferation, migration, and invasion capabilities. Additionally, it was observed that EGR-1 prompted G0/G1 arrest in OSCC cells by modulating the activity of cell cycle regulators.
These findings strongly support EGR-1's tumor-suppressive role in OSCC and hint at the potential for novel OSCC therapies aimed at restoring aberrant EGR-1 function.
口腔鳞状细胞癌(OSCC)具有显著的局部侵袭性和淋巴结转移倾向。鉴于其在晚期阶段的频繁检出以及随之而来的术后功能障碍,确定有效的早期检测和治疗分子标志物势在必行。早期生长反应因子-1(EGR-1)是一种在多种细胞类型中表达的多功能转录因子。其在癌症中的作用存在争议,既可以作为癌基因,也可以作为肿瘤抑制基因。
本研究进行了全面分析,包括大数据审查、使用50个OSCC样本的表达谱分析以及体外功能评估,以阐明EGR-1在OSCC中的作用。
比较分析显示,与健康对照或正常口腔黏膜相比,口腔癌组织中EGR-1表达显著降低。对多种OSCC细胞系进行的体外实验表明,EGR-1抑制细胞增殖、迁移和侵袭能力。此外,观察到EGR-1通过调节细胞周期调节因子的活性促使OSCC细胞停滞在G0/G₁期。
这些发现有力地支持了EGR-1在OSCC中的肿瘤抑制作用,并暗示了旨在恢复异常EGR-1功能的新型OSCC治疗方法的潜力。