Chou Chung-Hsien, Yen Chun-Han, Liu Chung-Ji, Tu Hsi-Feng, Lin Shu-Chun, Chang Kuo-Wei
Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Cancer Cell Int. 2024 Mar 25;24(1):115. doi: 10.1186/s12935-024-03301-9.
Oral squamous cell carcinoma (OSCC) is a prevalent neoplasm worldwide, necessitating a deeper understanding of its pathogenesis. VGF nerve growth factor inducible (VGF), a neuropeptide, plays critical roles in nerve and endocrine cell regulation.
In this study, the TCGA datasets were initially screened, identifying the upregulation of VGF in various malignancies. We focused on OSCC cell lines, identifying the suppressor mRNA miR-432-5p as a negative regulator of VGF. Additionally, we examined the prognostic value of VGF expression in OSCC tumors and its impact on cellular functions.
VGF expression was found to be an independent prognostic predictor in OSCC tumors. Cells expressing VGF exhibited increased oncogenicity, influencing the proliferation and migration of oral mucosal fibroblast. Transcriptome analysis revealed associations between VGF and various pathological processes, including malignancies, exosome release, fibrosis, cell cycle disruption, and tumor immune suppression. Moreover, IL23R expression, a favorable OSCC prognostic factor, was inversely correlated with VGF expression. Exogenous IL23R expression was found to suppress VGF-associated mobility phenotypes.
This study highlights the multifaceted role of VGF in OSCC pathogenesis and introduces the miR-432-5p-VGF-IL23R regulatory axis as a critical mediator. The combined expression of VGF and IL23R emerges as a potent predictor of survival in oral carcinoma cases, suggesting potential implications for future therapeutic strategies.
口腔鳞状细胞癌(OSCC)是一种在全球范围内普遍存在的肿瘤,有必要对其发病机制有更深入的了解。VGF神经生长因子诱导蛋白(VGF)作为一种神经肽,在神经和内分泌细胞调节中发挥着关键作用。
在本研究中,首先对TCGA数据集进行筛选,确定VGF在各种恶性肿瘤中上调。我们聚焦于OSCC细胞系,确定抑制性mRNA miR-432-5p是VGF的负调节因子。此外,我们研究了VGF表达在OSCC肿瘤中的预后价值及其对细胞功能的影响。
发现VGF表达是OSCC肿瘤的独立预后预测指标。表达VGF的细胞表现出更高的致癌性,影响口腔黏膜成纤维细胞的增殖和迁移。转录组分析揭示了VGF与各种病理过程之间的关联,包括恶性肿瘤、外泌体释放、纤维化、细胞周期紊乱和肿瘤免疫抑制。此外,IL23R表达作为OSCC的一个良好预后因素,与VGF表达呈负相关。发现外源性IL23R表达可抑制VGF相关的迁移表型。
本研究突出了VGF在OSCC发病机制中的多方面作用,并引入了miR-432-5p-VGF-IL23R调节轴作为关键介质。VGF和IL23R的联合表达成为口腔癌病例生存的有力预测指标,提示对未来治疗策略可能具有潜在意义。