SOX2-OT Binds with ILF3 to Promote Head and Neck Cancer Progression by Modulating Crosstalk between STAT3 and TGF-β Signaling.

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) ranks seventh among malignant tumors worldwide, with an estimated 500,000 new cases annually. Despite the development of early diagnosis technology, there are still 60% of patients already in the middle–late stages when they were first diagnosed with HNSCC. Despite advances in multidisciplinary synthetic therapy, the overall survival rate remains low, with a five-year survival rate of less than 50%. Thus, it is urgently needed to search for novel early diagnosis biomarkers and therapy targets. In this study, we revealed the role of SOX2-OT in HNSCC progression and metastasis by binding with ILF3, which may serve as a therapeutic target and prognostic biomarker to improve the early diagnosis and overall survival of HNSCC. Long non-coding RNA (lncRNA) is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The molecular mechanism of lncRNA SOX2-OT in HNSCC remains unclear. Therefore, we aimed to elucidate the oncogenic role of SOX2-OT in HNSCC. QRT-PCR analysis was performed in 61 pairs of HNSCC cancer tissues, adjacent normal tissues, and 68 plasma samples confirmed that lncRNA SOX2-OT was overexpressed in cancer tissues and plasma samples, which served as a poor prognostic factor for HNSCC. The FISH assay demonstrated that SOX2-OT was localized in the nucleus and cytoplasm of HNSCC cell lines. Further, the cell function assay confirmed that SOX2-OT promoted cell proliferation and metastasis in vitro and in vivo. RNA pulldown and RIP assay results revealed that SOX2-OT bonds with ILF3 in HNSCC, and the rescue assay confirmed that SOX2-OT played an oncogenic role depending on ILF3 protein expression. Ingenuity pathway analysis and Western blotting indicated that SOX2-OT regulated HNSCC progression by promoting STAT3 phosphorylation and modulating the crosstalk between STAT3 and TGF-β signaling. These results reveal evidence for the role of SOX2-OT in HNSCC progression and metastasis by binding to ILF3, which may serve as a therapeutic target and prognostic biomarker in HNSCC. [ABSTRACT FROM AUTHOR]