Paeonol inhibits the Glycolysis in oral squamous cell carcinoma though suppressing NAT10-mediated ac4C modification
Kang Yang1, Baosen Yue1, Huan Tian1
1Department of Pharmacy, Xi'an Hospital of Traditional Chinese Medicine, No.69, Fengcheng 8th Road, Weiyang District, Xi'an, 710021, China.
Background:
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral and maxillofacial regions. Paeonol, derived from Moutan Cortex, has diverse pharmacological effects including anti-inflammatory and anticancer activities. The N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification is a newly discovered RNA epigenetic mechanism. This study aimed to investigate the role of paeonol in OSCC and its underlying mechanisms of action.
Methods:
Cell viability and migration were assessed using a cell counting kit-8 and transwell migration assays. Glycolysis-related indices were detected using commercial kits. The interaction between NAT10 and hexokinase 2 (HK2) was examined using RNA immunoprecipitation and dual-luciferase reporter assays. A tumor-bearing mouse model was established.
Results:
The results showed that paeonol treatment decreased the viability, migration, and glycolysis of OSCC cells. Moreover, paeonol treatment inhibited NAT10-mediated ac4C modifications in OSCC cells. In addition, NAT10 overexpression upregulates glycolysis and cell migration in OSCC cells. Moreover, NAT10 upregulated ac4C levels of HK2 in OSCC cells. Animal studies have revealed that paeonol treatment decreases OSCC tumor growth.
Conclusion:
This study revealed that paeonol inhibited glycolysis and cell migration in OSCC by suppressing the NAT10-mediated ac4C modification of HK2.
Insights
Paeonol, a natural compound, inhibits oral cancer progression by targeting the NAT10-mediated RNA modification pathway. This study demonstrates paeonol
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy.
- Paeonol exhibits anti-inflammatory and anticancer properties.
- N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac⁴C) modification is an emerging RNA epigenetic mechanism.
Purpose of the Study:
- To investigate paeonol's therapeutic potential in OSCC.
- To elucidate the underlying molecular mechanisms involving NAT10 and ac⁴C modification.
Main Methods:
- Assessed cell viability, migration, and glycolysis.
- Examined NAT10-mediated ac⁴C modification and its interaction with hexokinase 2 (HK2).
- Utilized cell-based assays, RNA immunoprecipitation, dual-luciferase reporter assays, and a mouse model.
Main Results:
- Paeonol reduced OSCC cell viability, migration, and glycolysis.
- Paeonol inhibited NAT10-mediated ac⁴C modifications.
- NAT10 overexpression enhanced glycolysis and migration, and upregulated ac⁴C levels of HK2.
- Paeonol treatment suppressed OSCC tumor growth in vivo.
Conclusions:
- Paeonol inhibits OSCC progression by suppressing NAT10-mediated ac⁴C modification of HK2.
- This pathway impacts glycolysis and cell migration in OSCC.
- Paeonol represents a potential therapeutic agent for OSCC.
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