LUCAT1 promotes stemness in head and neck squamous cell carcinoma by sponging miR-128

Head and neck squamous cell carcinoma (HNSCC) progression is well documented to be predominantly driven by a small subset of cancer stem cells (CSCs). These CSCs are implicated in recurrence, metastasis, dormancy, and therapy resistance. Therefore, targeting cancer stem cells has inspired the design of innovative treatment strategies. This study demonstrates that knockdown of the long non-coding RNA (lncRNA) LUCAT1 markedly reduces cancer cell stemness. This effect was confirmed across several experimental assays, including sphere-forming capacity and in vitro limiting dilution assays. Consequently, LUCAT1 knockdown potently suppresses HNSCC progression. Mechanistically, LUCAT1 functions as a competing endogenous RNA (ceRNA) to sponge miR-128, thereby relieving the post-transcriptional repression of downstream targets and promoting oncogenesis. Functional rescue assays show that restoration of miR-128 significantly reverses the antitumor efficacy of LUCAT1 knockdown on HNSCC cell. Moreover, miR-128 also attenuates the antitumor efficacy of LUCAT1 knockdown in both subcutaneous xenograft models and lymph node metastasis models in vivo. In agreement with previous results, BMI1 was identified as a direct and functionally relevant target of miR-128 in HNSCC cells. Collectively, these findings show that LUCAT1 constitutes a key regulatory component within the cancer stemness regulatory network of HNSCC, and underscores the function of the LUCAT1/miR-128 axis in sustaining stem cell-like traits and driving HNSCC malignant progression.