Dissecting the role of LINC00504 and LINC00520 in melanoma phenotype switching

Melanoma is an aggressive and deadly type of skin cancer with an increase incidence worldwide. It presents a complex challenge in oncology due to its inherent heterogeneity, driven in part by its remarkable plasticity. This phenomenon is associated with phenotype switching and significantly impacts disease progression and therapeutic response, with the “proliferative” phenotype generally exhibiting greater sensitivity to treatment compared to the “invasive” phenotype. Understanding the molecular mechanisms underlying melanoma phenotype switching is crucial for devising more effective therapeutic strategies. Our study aims to elucidate the intricate mechanisms driving melanoma phenotype switching, with a particular focus on the role of long non-coding RNAs (lncRNAs). By analysing the functions of these regulatory molecules in mediating the switch between proliferative and invasive phenotypes, 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. Utilizing a combination of bioinformatics analyses and experimental approaches, including RNA pulldown assays, RNA interference and other functional assays, we investigated the molecular mechanisms by which these lncRNAs act as miRNA sponges and modulate melanoma behavior. Our investigations uncovered a pivotal role for LINC00504 and LINC00520 in melanoma phenotype dynamics. Silencing of these lncRNAs resulted in perturbations across multiple regulatory layers, including upregulation of miRNA expression, modulation of target mRNA abundance, and consequential downregulation in protein levels. Moreover, silencing of lncRNA correlated with diminished migratory potential, underscoring the importance of these regulatory molecules in influencing melanoma dynamics. By elucidating the complex interplay between non-coding RNAs and phenotypic plasticity in melanoma, our findings underscore the potential of lncRNAs as diagnostic biomarkers of proliferative phenotype and therapeutic targets in this deadly disease. Moreover, our study offers valuable insights into the underlying mechanisms of phenotype switching, paving the way for the development of more personalized and efficacious treatment strategies for melanoma patients.