Journal of stomatology, oral and maxillofacial surgery · 2025
LncRNA HNF1A-AS1 inhibits ferroptosis in oral squamous cell carcinoma cells through the miR-124/ PKM2 axis.
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Deng Lu, Tang Qiang, Lv Huiqin, Liu Zhe
Аннотация
OBJECTIVES: The aim of this study was to illustrate the molecular mechanism of lncRNA HNF1A-AS1 in ferroptosis in OSCC, providing novel therapeutic implications for OSCC treatment.
METHODS: Human OSCC cell lines (CAL-27, SCC-15, HSC-3, WSU-HN12) and normal human oral keratinocytes (NHOK) were used for in vitro experiments. The function of lncRNA HNF1A-AS1 on ferroptosis in OSCC was evaluated through measurement of cell proliferation, gene expression, protein expression levels, and ferroptosis-related indicators. The binding relationships between miR-124 and HNF1A-AS1, as well as between miR-124 and the 3'UTR of PKM2, were verified using dual-luciferase reporter gene assays and RIP assays. miR-124 inhibition or PKM2 overexpression was combined with silencing of HNF1A-AS1 for functional verification. Statistical analysis was performed to compare changes in the indicators among different treatments.
RESULTS: In OSCC cells, HNF1A-AS1 and PKM2 were overexpressed, while miR-124 expression was downregulated. Silencing HNF1A-AS1 suppressed cell proliferation, elevated contents of ROS, MDA and Fe2+, reduced GSH content, enhanced ACSL4 expression and diminished GPX4 expression. Mechanistically, HNF1A-AS1 bound to and sequestered miR-124, and miR-124 bound to and inhibited PKM2 expression. Both miR-124 inhibition and PKM2 overexpression partially reversed the promotive effect of HNF1A-AS1 silencing on OSCC cell ferroptosis.
CONCLUSION: HNF1A-AS1 inhibits OSCC cell ferroptosis by binding to miR-124 to relieve the transcriptional inhibition of PKM2. Our study offers a potential therapeutic strategy for OSCC treatment.
METHODS: Human OSCC cell lines (CAL-27, SCC-15, HSC-3, WSU-HN12) and normal human oral keratinocytes (NHOK) were used for in vitro experiments. The function of lncRNA HNF1A-AS1 on ferroptosis in OSCC was evaluated through measurement of cell proliferation, gene expression, protein expression levels, and ferroptosis-related indicators. The binding relationships between miR-124 and HNF1A-AS1, as well as between miR-124 and the 3'UTR of PKM2, were verified using dual-luciferase reporter gene assays and RIP assays. miR-124 inhibition or PKM2 overexpression was combined with silencing of HNF1A-AS1 for functional verification. Statistical analysis was performed to compare changes in the indicators among different treatments.
RESULTS: In OSCC cells, HNF1A-AS1 and PKM2 were overexpressed, while miR-124 expression was downregulated. Silencing HNF1A-AS1 suppressed cell proliferation, elevated contents of ROS, MDA and Fe2+, reduced GSH content, enhanced ACSL4 expression and diminished GPX4 expression. Mechanistically, HNF1A-AS1 bound to and sequestered miR-124, and miR-124 bound to and inhibited PKM2 expression. Both miR-124 inhibition and PKM2 overexpression partially reversed the promotive effect of HNF1A-AS1 silencing on OSCC cell ferroptosis.
CONCLUSION: HNF1A-AS1 inhibits OSCC cell ferroptosis by binding to miR-124 to relieve the transcriptional inhibition of PKM2. Our study offers a potential therapeutic strategy for OSCC treatment.