The miR-876-5p/SOCS4/STAT3 pathway induced the expression of PD-L1 and suppressed antitumor immune responses.

Oral squamous cell carcinoma (OSCC) remains a formidable challenge due to its high recurrence rates and poor prognosis. This study focuses on miR-876, a microRNA significantly associated with OSCC recurrence and clinical outcomes. Analysis of miRNA expression profiles from recurrent OSCC patients revealed that miR-876-5p is markedly upregulated in recurrent tumor tissues and the high expression of miR-876-5p correlates with reduced disease-free and overall survival. Functional assays demonstrated that miR-876 enhances OSCC cell growth, migration, and stemness, contributing to chemoresistance. Mechanistically, miR-876-5p directly targets SOCS4, leading to increased STAT3 activation and subsequent upregulation of PD-L1, which facilitates immune evasion. Additionally, exposure to the tobacco-specific carcinogen NNK was found to induce miR-876 expression and STAT3 activation, implicating environmental factors in miR-876 regulation and promote cancer recurrent. These findings identify the miR-876-5p-SOCS4-STAT3 axis as a critical pathway in OSCC progression, highlighting miR-876-5p as a potential biomarker and therapeutic target to improve treatment outcomes in OSCC patients.