ArticleClinical and translational medicine2022
N6-methyladenosine reader YTHDF3 regulates melanoma metastasis via its 'executor'LOXL3.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Activation of MyD88/IRAK1 axis and downstream proinflammatory signaling in healthy adult and neonatal African American skin.JID innovations : skin science from molecules to population health · 2026Article
- BGN/MDK Axis in the Melanoma Tumor Microenvironment Strengthens Tumor Malignancy by Modulating Cancer Cells and Cancer-Associated Fibroblasts Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms and therapeutic potential of YTHDF readers: Linking epitranscriptomics to cancer.Journal of pharmaceutical analysis · 2026Review
- m6A RNA Methylation Promotes the Melanoma Metastasis Mediated by Extracellular VesicleCancers · 2026Article
- YTHDF3 Promoted Gastric Cancer Progression by Facilitating mAnalytical cellular pathology (Amsterdam) · 2026Article
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- mActa pharmaceutica Sinica. B · 2025Review
- [Role of m6A methylation modification in photoaging and ultraviolet-induced skin cancers].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- WTAP Suppresses Cutaneous Melanoma Progression by Upregulation of KLF9: Insights into m6A-Mediated Epitranscriptomic Regulation.Biomedicines · 2025Article
- mMolecules (Basel, Switzerland) · 2025Review
- The Role of Lysyl Oxidase in the Pathological Stage of Atherosclerosis: Structural Stabilizer or Disease Driver?Current atherosclerosis reports · 2025Review
- LOXL3 Silencing Hampers the Metastasis and Angiogenesis of Gastric Cancer Cells Dependent on Ferroptosis Activation.Molecular biotechnology · 2025Article
- The mRNA (New York, N.Y.) · 2025Article
- RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.Journal of advanced research · 2025Article
- METTL3 Promotes Cutaneous T-Cell Lymphoma Progression by Regulating ARHGEF12 Expression.International journal of molecular sciences · 2025Article
- MTHFD2 stabilizes LOX expression through RNA methylation modification to promote sepsis-induced acute kidney injury progression.Human cell · 2025Article
- Exploring the methyl-verse: Dynamic interplay of epigenome and m6A epitranscriptome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Integrating bulk and single-cell RNA sequencing data: unveiling RNA methylation and autophagy-related signatures in chronic obstructive pulmonary disease patients.Scientific reports · 2025Article
- Gene expression profiling of SPIN1 in gastric cancer: insights into tumorigenesis and potential therapeutic targets.Frontiers in genetics · 2025Article
- Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA number of studies have demonstrated that N6-methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive.
methodsRT-qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase-like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi-omics analysis including RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR and CRISPR-Cas13b-based epitranscriptome engineering.
resultsIn this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA-binding protein 7 (CHD7) were identified by means of RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses. Besides, RT-qPCR, Western blot, RIP-qPCR and MeRIP-qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR-Cas13b-based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation.
conclusionsThe YTHDF3-LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.
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