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ac4C acetylation regulates mRNA stability and translation efficiency in osteosarcoma
Wenjie Zhang1, Jia Gao1, Lei Fan1
1Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, PR China.
Heliyon
|July 24, 2023
Summary
Inhibition of N4-acetylcytidine (ac4C) acetylation in osteosarcoma cells using Remodelin suppressed cell proliferation and metastasis. This treatment also promoted apoptosis and cell cycle arrest, highlighting ac4C's role in gene expression.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- N4-acetylcytidine (ac4C) acetylation enhances target gene expression by increasing mRNA stability.
- Osteosarcoma is a significant bone cancer with a need for novel therapeutic targets.
- The role of ac4C acetylation in osteosarcoma progression remains largely unexplored.
Purpose of the Study:
- To investigate the functional role of ac4C acetylation in osteosarcoma.
- To determine the effects of inhibiting N-acetyltransferase 10 (NAT10) on osteosarcoma cell behavior.
- To identify target genes regulated by ac4C acetylation in osteosarcoma.
Main Methods:
- Osteosarcoma cell lines (U2OS, MG63) were treated with the NAT10 inhibitor Remodelin.
- Cell proliferation was assessed using CCK8 assays.
- Cell cycle, apoptosis, and invasion were analyzed by flow cytometry and Transwell assays, respectively.
- ac4C acetylation targets were identified using acetylated RNA immunoprecipitation and sequencing (acRIP-seq).
- Gene and protein expression were validated by RT-PCR and Western blot.
Main Results:
- Remodelin treatment inhibited NAT10 expression and osteosarcoma cell proliferation.
- Significant increases in G1 phase cells and apoptosis were observed, with a decrease in S phase cells.
- Cell invasiveness was significantly reduced following Remodelin treatment.
- The farnesyltransferase subunit beta (FNTB) gene was identified as a direct target of ac4C acetylation.
Conclusions:
- Inhibition of ac4C acetylation effectively suppresses osteosarcoma cell proliferation and metastasis.
- Targeting ac4C acetylation promotes apoptosis and induces cell cycle arrest in osteosarcoma.
- ac4C acetylation is crucial for maintaining the stability and translation efficiency of target gene mRNA in osteosarcoma.
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