SAMMSON lncRNA: A Critical Link in Melanoma Development and Therapeutic Resistance

Malignant melanoma is one of the most aggressive malignancies and has a strong tendency to metastasize in the early stages of the disease. Although Melanoma accounts for less than ۱۰% of skin malignancies, the mortality rate is as high as ۸۰% [۱]. UV radiation is the main environmental risk factor in melanoma pathogenesis. Furthermore, host factors such as family history, and genetic predisposition, have a major role in melanoma development [۲]. The genomic cause of melanoma can be classified according to mutations that patients harbor in their cells. The molecular subtype of BRAF gene mutations is responsible for ۵۰% of melanoma patients and from all BRAF-mutant individuals, about ۹۰% harbor the specific V۶۰۰ mutation which activates the MAPK-ERK pathways constitutively, allowing cells to become self-sufficient in growth signals and leads to tumor formation [۳]. Current melanoma therapeutic approaches including surgery, radiotherapy, chemotherapy, and immunotherapy, often have limited efficacy due to high drug resistance and adverse effects. The transformation of a benign nevus into melanoma is governed by a complex molecular network, highlighting the need to understand the molecular mechanisms underlying melanoma formation better and to identify new therapeutic targets. [۴]. Recently, many studies have revealed the close association of long noncoding RNAs (lncRNAs) with the development of many cancers, including melanoma [۵]. lncRNAs are a group of non-coding RNAs containing ۲۰۰ nucleotides and above without protein-coding potential. LncRNAs may have pivotal roles in various biological mechanisms, including proliferation, cell cycle, apoptosis, angiogenesis, metastasis, and invasion through different cascades [۲]. LncRNAs are promising targets for selective anticancer therapies due to their specific expression profiles in other cell types and diseases. Objectives: This review focuses on the role of lncRNAs in contributing to drug resistance in melanoma, aiming to identify potential biomarkers and therapeutic targets. Material and methods: In this review, we performed a web search in PubMed using the keywords “Melanoma [Mesh] AND RNA, Long Noncoding [Mesh]” and selected articles published after ۲۰۲۰ to identify potential biomarkers against melanoma. Results: The study by Leucci et al. identified the lineage-specific lncRNA SAMMSON as a critical player in melanoma. SAMMSON, a direct transcriptional target of SOX۱۰, is expressed in over ۹۰% of human melanoma patients, including both primary and metastatic melanoma, but not in normal melanocytes, nevi, or any other normal adult tissues that were profiled. Strikingly, SAMMSON is required for the growth of melanoma cells. Knock-down of SAMSON resulted in cell death of melanoma independently of their NRAS, BRAF, or TP۵۳ status. Moreover, melanoma cells with acquired resistance to BRAF inhibitors (BRAFi) remain sensitive to this treatment and SAMMSON knockdown synergized with BRAFi and MEKi in killing BRAFV۶۰۰E-melanoma cells. [۶]. Conclusion: SAMMSON knock-down induces cell death in melanoma independently of key oncogenic mutations and enhances the efficacy of BRAFi and MEKi therapies in BRAFV۶۰۰E mutant melanoma. Therefore, SAMMSON holds promise as both a novel biomarker and a highly selective therapeutic target in melanoma treatment.

کلیدواژه ها:

Skin Cancer ، Melanoma ، Melanogenesis ، non coding RNA