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Int J Biol Sci 2024; 20(5):1729-1743. doi:10.7150/ijbs.92994 This issue Cite

Research Paper

ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner

Hanwen Wang#, Shixin Zhao#, Hengdeng Liu#, Yiling Liu, Zihui Zhang, Ziheng Zhou, Peng Wang, Shaohai Qi, Julin Xie✉

Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People's Republic of China.
#Equal contribution.

✉ Corresponding author: Julin Xie, xiejulinsysu.edu.cn.

Citation:
Wang H, Zhao S, Liu H, Liu Y, Zhang Z, Zhou Z, Wang P, Qi S, Xie J. 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; 20(5):1729-1743. doi:10.7150/ijbs.92994. https://www.ijbs.com/v20p1729.htm
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Abstract

Graphic abstract

Background: 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. This study analyzed 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.

Methods: Based on public databases, the m6A-related gene expression landscape in SKCM was portrayed. MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5. In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-m6A-ABCA1 axis in SKCM.

Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis. ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo. We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m6A demethylation. Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m6A-dependent manner.

Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM, suggesting the ALKBH5-m6A-ABCA1 axis as a potential therapeutic target in SKCM.

Keywords: Skin cutaneous melanoma, N6-methyladenosine methylation, Alkylation repair homolog protein 5, ATP-binding cassette transporter A1, Autophagy

Citation styles

APA
Wang, H., Zhao, S., Liu, H., Liu, Y., Zhang, Z., Zhou, Z., Wang, P., Qi, S., Xie, J. (2024). ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner. International Journal of Biological Sciences, 20(5), 1729-1743. https://doi.org/10.7150/ijbs.92994.

ACS
Wang, H.; Zhao, S.; Liu, H.; Liu, Y.; Zhang, Z.; Zhou, Z.; Wang, P.; Qi, S.; Xie, J. 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, 20 (5), 1729-1743. DOI: 10.7150/ijbs.92994.

NLM
Wang H, Zhao S, Liu H, Liu Y, Zhang Z, Zhou Z, Wang P, Qi S, Xie J. 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; 20(5):1729-1743. doi:10.7150/ijbs.92994. https://www.ijbs.com/v20p1729.htm

CSE
Wang H, Zhao S, Liu H, Liu Y, Zhang Z, Zhou Z, Wang P, Qi S, Xie J. 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. 20(5):1729-1743.

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