Study of the role of the lncRNA LADON in melanoma tumour progression

LADON is a long non-coding RNA and natural antisense transcript of the NODAL gene, identified by the Collignon team during their investigation of the latter in melanoma progression. In line with findings from other groups, they showed that NODAL is not expressed in melanoma. Instead, they discovered that the tumour-promoting activity previously attributed to NODAL is mediated by LADON. LADON expression increases over four days in culture, promoting the mesenchymal-to-amoeboid transition, a process critical to melanoma invasiveness. However, the precise mechanism by which LADON exerts its effects remains unclear. Furthermore, previous studies focused on exon 2 deletion, leaving the role of other regions unexplored. To address this, we deleted the full LADON locus and observed strong effects on cell proliferation, morphology, and migration, often more pronounced than with exon 2 deletion, suggesting critical roles for exon 2-flanking regions. Proteomic analysis revealed that LADON modulates Rho/ROCK and Rac1 pathways, leading to features consistent with amoeboid migration. Additionally, we found that the 3' region of LADON might exert a repressive effect on its own transcription. These findings highlight LADON as a key player in melanoma progression and the need for deeper investigation into its full-length structure and molecular function.