Abstract
BACKGROUND/PURPOSE: Oral squamous cell carcinoma (OSCC) remains a significant challenge with a high recurrence rate and metastasis, which are believed to be driven by cancer stem cells (CSCs). The long non-coding RNA LINC00704 has been implicated in the malignant progression of various cancers. This study aimed to investigate the critical role for LINC00704 in oral cancer stemness. MATERIALS AND METHODS: The clinical significance of LINC00704 was determined in our OSCC cohort and the TCGA-HNSC dataset. Silencing of LINC00704 in OCSCs was established by lentiviral-mediated RNA interference. Cellular ALDH activity, stemness markers expression, and sphere formation ability were assessed to evaluate cancer stemness, while cell migration, colony formation, and apoptosis were measured to determine malignancy. A luciferase reporter assay and microRNA inhibitor transfection were conducted to validate the molecular function of LINC00704. RESULTS: The present study demonstrated that LINC00704 was significantly upregulated in OSCC tumors compared to paired normal mucosa and that its elevated expression positively correlated with advanced staging and poor survival in HNSC patients. LINC00704 knockdown in OCSCs significantly diminished their stemness, evidenced by reduced ALDH activity, decreased expression of stemness markers, and impaired migration and colony formation capabilities. Mechanistically, miR-204 was demonstrated to direct interact with LINC00704 3'UTR. Furthermore, inhibition of miR-204 attenuated the effects of LINC00704 knockdown on suppressing self-renewal and inducing apoptosis in OCSCs. CONCLUSION: This study revealed that LINC00704 functions as a miR-204 sponge to promote the cancer stemness and malignancy of OCSCs, highlighting the LINC00704/miR-204 axis as a novel and potentially therapeutic target for OSCC.