Oncogenic miR-182-5p Targets NCOA4 to Disrupt the NCOA4-FTH1 Axis-Mediated Ferroptosis in Head and Neck Squamous Cell Carcinoma.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by a high recurrence rate and poor prognosis. Ferroptosis, a regulated cell death, plays a significant role in inhibiting tumor progression. However, its role and regulatory mechanisms in HNSCC remain unclear. In this study, the expression of ferroptosis-related molecules in HNSCC is analysed and NCOA4 and FTH1 are identified as prognostic markers. TU177 and TU686 cells are transfected with plasmids for the overexpression or knockdown of NCOA4 and FTH1. MTT assays demonstrated reduced cell viability following either NCOA4 overexpression or FTH1 knockdown alone. Concurrently, ferroptosis hallmarks such as iron overload and ROS overproduction are upregulated in these conditions. Conversely, NCOA4 knockdown or FTH1 overexpression has the opposite effects. Furthermore, miR-182-5p is found to be significantly upregulated in HNSCC tissues. Mechanistic studies revealed that miR-182-5p directly binding to the NCOA4 3' UTR, leading to the downregulation of NCOA4 expression and suppression of NCOA4/FTH1-mediated ferroptosis. In conclusion, the finding elucidate the role of miR-182-5p/NCOA4/FTH1 signaling axis in regulating ferroptosis in HNSCC and provide insights into the molecular mechanism underlying ferroptosis in HNSCC cells.