m6A modification is one of the most important post-transcriptional modifications in RNA and plays an important role in promoting translation or decay of RNAs. The role of m6A modifications has been highlighted by increasing evidence in various cancers, which, however, is rarely explored in acral melanoma. Here, we demonstrated that m6A level was highly elevated in acral melanoma tissues, along with the expression of METTL3, one of the most important m6A methyltransferase. Besides, higher expression of METTL3 messenger RNA (mRNA) correlated with a higher stage in primary acral melanoma patients. Knockdown of METTL3 decreased global m6A level in melanoma cells. Furthermore, METTL3 knockdown suppressed the proliferation, migration, and invasion of melanoma cells. In METTL3 knockdown xenograft mouse models, we observed decreased volumes and weights of melanoma tissues. Mechanistically, we found that METTL3 regulates certain m6A-methylated transcripts, thioredoxin domain containing protein 5 (TXNDC5), with the confirmation of RNA-seq, MeRIP-seq, and Western blot. These data suggest that METTL3 may play a key role in the progression of acral melanoma, and targeting the m6A dependent-METTL3 signaling pathway may serve as a promising therapeutic strategy for management of patients of acral melanomas.
Ferroptosis is a newly discovered form of non-apoptotic cell death that relies on iron-mediated oxidative damage, playing a crucial role in the progression and therapy resistance of melanoma. Hence, the potential value of ferroptosis-related genes (FRGs) as a prognostic model and therapeutic target in melanoma requires further investigation. In this study, the relationship between FRGs and melanoma was revealed by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO). A 6-FRGs signature was constructed by Univariate, multivariate, and lasso Cox regression analyses in the TCGA cohort. The GEO database was used to validate the efficacy of the signature. The protein and mRNA expression level of the signature genes were examined in real-world melanoma tissues via immunohistochemical and quantificational real-time polymerase chain reaction (qRT-PCR). Functional enrichment analysis and immune-related analysis were conducted to identify the potential biological functions and pathways of the signature. Ten putative small molecule drugs were predicted by Connectivity Map (CMAP). As a result, a 6-FRGs signature was constructed to stratify melanoma patients into two risk groups. Compared with the low-risk group, patients in the high-risk group had a worse prognosis and a lower ImmuneScore. Immune-related pathways were enriched in the low-risk group. Immune Function and immune cell infiltration of the low-risk group were significantly higher than that of the high-risk group. The differential expression of these six FRGs in melanoma and adjacent normal tissues was confirmed. Moreover, higher expression of immune checkpoint molecules and a greater sensitivity to immunotherapy were observed in the low-risk group. Some small molecular drugs in the CMAP database hold the potential to treat melanoma. Overall, we identified a novel FRGs signature for prognostic prediction in melanoma. Based on the signature-related immune infiltration landscape found in our study, targeting the FRGs might be a therapeutic alternative for melanoma.
Introduction: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, and its pathogenesis might relate to ultraviolet light and Merkel cell polyomavirus infection. MCC in the Chinese population is uncommon.Here, we present a case of MCC that occurred based on widespread actinic keratosis (AK) in a Chinese female.Case report: An 82-year-old woman presented with two rapidly enlarging and rupture lesions on the face for 1 year. Biopsy was suggestive of squamous cell carcinoma (SCC) on the forehead and MCC on the left cheek. The patient had a history of generalized AK for 3 years. The lesion on the left cheek was also revealed as an AK by histopathological examination 1 year ago. Complete surgical resection was performed to remove the two malignancies.Discussion: The co-occurrence of AK, SCC, and MCC in a Chinese woman is unusual. Immunohistopathological examination is vital for correct diagnosis. The three tumors, in this case, may originate from two different precursor cells and are affected by the same carcinogen. Alternatively, they may come from the same pluripotent epidermal stem cells, and chronic exposure to ultraviolet light and Merkel cell polyomavirus lead to the formation of different types of tumors. The coexist of MCC with other cutaneous tumors provided a train of thought for exploring the origin of MCC. Conclusion:We reported a rare co-existence phenomenon of MCC associated with AK and SCC. Hence, longterm follow-up and early treatment are imperative for patients with premalignant lesions, such as widespread AK.
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