Abstract：
Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.
摘要：
维甲酸受体相关孤儿受体α（RORα），在一系列人类恶性肿瘤中，一种必需的肿瘤抑制剂，被归类为孤儿核受体家族的成员。口腔癌最常见的形式，舌鳞状细胞癌（TSCC）的特征是其严重的恶性和预后不良。然而,其肿瘤发生机制与RORα表达水平相关的程度尚不完全清楚.这项研究的目的是研究RORα参与TSCC的分子机制。通过使用免疫组织化学（IHC），发现在本研究中,与邻近的正常组织相比,RORα的表达水平在TSCC组织中显著下调。为了进一步研究RORα在TSCC中的作用，我们通过转染RORαcDNA并使用选择性RORα激动剂SR1078激活了RORα在人TSCC细胞系（SCC9细胞）中的表达。结果表明,RORα能显著抑制其侵袭,迁移,扩散,和TSCC细胞粘附并诱导细胞凋亡。此外,异种移植模型证实了以下结论：稳定激活或用SR1078处理以增加RORα含量可显着抑制肿瘤的生长和发展。一起来看,本研究为RORα在TSCC进展中的抑制作用提供了有力的证据。此外,SR1078在TSCC中的初步应用结果表明，SR1078有望成为TSCC的潜在治疗药物。这些发现为TSCC治疗的潜在生物标志物和药物的开发提供了创新的观点。目的是介绍预防和治疗TSCC的新策略和替代方法。
