KEY TAKEAWAYS
- The study aimed to explore ALKBH5’s role in mediating m6A modification and its mechanism in SKCM.
- Researchers noticed the vital role of ALKBH5-mediated m6A modification in SKCM progression, identifying the ALKBH5-m6A-ABCA1 axis as a promising therapeutic target.
N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear.
Hanwen Wang and the team aimed to analyze the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and its potential mechanism in human SKCM.
Researchers performed an inclusive analysis of the m6A-related gene expression landscape in SKCM utilizing public databases. MeRIP-Seq and RNA-Seq methodologies were employed to identify the downstream targets of ALKBH5, a key demethylase involved in m6A modification. In-depth in vivo and in vitro functional phenotype experiments were conducted, alongside rescue functional experiments, to elucidate the mechanism underlying the ALKBH5-m6A-ABCA1 axis in SKCM.
ALKBH5 was found to be upregulated in SKCM and was associated with poor prognosis. In vitro experiments revealed that ALKBH5 promoted melanoma cell proliferation, colony formation, migration, and invasion while inhibiting autophagy, thus facilitating tumor growth and metastasis in vivo.
Additionally, ABCA1, a membrane protein involved in cholesterol efflux, was identified as a downstream target of ALKBH5-mediated m6A demethylation. Furthermore, data demonstrated that ALKBH5 promoted SKCM by mediating ABCA1 downregulation, reducing ABCA1 mRNA stability in an m6A-dependent manner.
The study concluded that the functional significance of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM highlights the ALKBH5-m6A-ABCA1 axis as a potential therapeutic target in SKCM.
The study was supported by the National Natural Science Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38481816/
Wang H, Zhao S, Liu H, et al. (2024). “ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner.” Int J Biol Sci. 2024 Feb 25;20(5):1729-1743. doi: 10.7150/ijbs.92994. PMID: 38481816; PMCID: PMC10929202.
