ALKBH5 promotes the progression of infantile hemangioma through regulating the NEAT1/miR-378b/FOSL1 axis
- PMID: 35182329
- DOI: 10.1007/s11010-022-04388-2
ALKBH5 promotes the progression of infantile hemangioma through regulating the NEAT1/miR-378b/FOSL1 axis
Abstract
Our work aims to investigate long non-coding RNA (lncRNA) N6-methyladenosine (m6A) modification and its role in infantile hemangioma (IH). The mRNA and protein expression levels were assessed using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Me-RIP assay was performed to evaluate lncRNA NEAT1 m6A levels. Cell proliferation, migration and invasion were evaluated using cell counting kit-8 assay, transwell migration and invasion assay, respectively. Photo-activatable ribonucleoside-enhanced crosslinking and immunoprecipitation assay was conducted to verify the binding relationship between lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) and ALKBH5 (an RNA demethylase). The binding relationship between lncRNA NEAT1, microRNA (miR)-378b and FOS-like antigen 1 (FOSL1) was verified using dual-luciferase reporter gene assay and/or RNA immunoprecipitation assay. ALKBH5, lncRNA NEAT1 and FOLS1 expression was elevated in IH tissues, while miR-378b was downregulated. ALKBH5 knockdown suppressed cell proliferation, migration and invasion of IH cells, while promoting cell apoptosis. ALKBH5 promoted lncRNA NEAT1 expression by reducing the m6A modification of lncRNA NEAT1. In addition, miR-378b was the target of lncRNA NEAT1, and its overexpression reversed the promotion effect of lncRNA NEAT1 overexpression on IH cell tumor-like behaviors. Moreover, FOLS1 was the target of miR-378b, and its overexpression reversed the inhibitory effect of miR-378b overexpression on IH cell tumor-like behaviors in vitro. ALKBH5 might have great potential as therapeutic target for IH, since ALKBH5 silencing suppressed IH progression by regulation of the NEAT1/miR-378b/FOSL1 axis.
Keywords: ALKBH5; FOSL1; Infantile hemangioma; MiR-378b; lncRNA NEAT1; m6A modification.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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References
-
- Solman L, Glover M, Beattie PE, Buckley H, Clark S, Gach JE, Giardini A, Helbling I, Hewitt RJ, Laguda B, Langan SM, Martinez AE, Murphy R, Proudfoot L, Ravenscroft J, Shahidullah H, Shaw L, Syed SB, Wells L, Flohr C (2018) Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines. Br J Dermatol 179:582–589. https://doi.org/10.1111/bjd.16779 - DOI - PubMed
-
- Léauté-Labrèze C, Harper JI, Hoeger PH (2017) Infantile haemangioma. Lancet 390:85–94. https://doi.org/10.1016/s0140-6736(16)00645-0 - DOI - PubMed
-
- Smith CJF, Friedlander SF, Guma M, Kavanaugh A, Chambers CD (2017) Infantile hemangiomas: an updated review on risk factors, pathogenesis, and treatment. Birth Defects Res 109:809–815. https://doi.org/10.1002/bdr2.1023 - DOI - PubMed
-
- Roundtree IA, Evans ME, Pan T, He C (2017) Dynamic RNA modifications in gene expression regulation. Cell 169:1187–1200. https://doi.org/10.1016/j.cell.2017.05.045 - DOI - PubMed - PMC
-
- Nilsen TW (2014) Molecular biology. Internal mRNA methylation finally finds functions. Science 343:1207–1208. https://doi.org/10.1126/science.1249340 - DOI - PubMed
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