Dissecting the role of non-coding RNAs in melanoma phenotype switching

Melanoma is an aggressive and deadly skin cancer that presents a complex challenge in oncology due to its phenotypic plasticity. This ability to switch between different phenotypic states significantly impacts disease progression and treatment response. The main phenotypes are called “proliferative” and “invasive” phenotypes, and generally invasive cells exhibit drug resistance. Understanding the molecular mechanisms underlying this phenomenon is crucial for developing more effective therapies. Our study focused on the role of long non-coding RNAs (lncRNAs) in mediating melanoma phenotype switching. By analysing their function, we seek to identify potential therapeutic targets and biomarkers for optimizing melanoma treatment strategies. Transcriptomic profiling of melanoma primary cells identified LINC00504 and LINC00520 as highly expressed lncRNAs associated with proliferative phenotype. Through bioinformatics and experimental approaches, including RNA pulldown assays, RNA interference and other functional assays, we investigated how these lncRNAs act as miRNA sponges to modulate melanoma behaviour. Our findings revealed a pivotal role for these lncRNAs in melanoma phenotype dynamics. Silencing these lncRNAs disrupted multiple regulatory layers, including miRNA expression, target mRNA abundance, and protein levels. This correlated with diminished migratory potential, highlighting the importance of lncRNAs in influencing melanoma behaviour. Our results underscore the potential of lncRNAs as diagnostic biomarkers and therapeutic targets for melanoma. By elucidating the complex interplay between non-coding RNAs and phenotypic plasticity, our study paves the way for developing more personalized and effective treatment strategies for melanoma patients.