Retinoic acid receptor-related orphan receptor alpha and synthetic RORalpha agonist against invasion and metastasis in tongue squamous cell carcinoma.

Retinoic acid receptor-related orphan receptor alpha (RORalpha), 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 RORalpha expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORalpha is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORalpha was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORalpha in TSCC, we activated the expression of RORalpha in human TSCC cell line (SCC9 cells) by transfecting RORalpha cDNA and using the selective RORalpha agonist SR1078. The results show that RORalpha 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 RORalpha content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORalpha 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.