Contribution of osmotic stress and long non codings RNAs to drug tolerance in melanoma

Long non-coding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with no coding potential. They are involved in the regulation of epigenetic and post-transcriptional events and growing evidence indicates the link between lncRNAs aberrant expression and cancer development and resistance to therapy. One pending question is how such poorly expressed transcripts impacts the activity of multiple and often abundant proteins. There is recent evidence that osmotic stress, which affects the cellular protein concentration and interaction, induces phenotype switching of cancer cells into an invasive and drug-tolerant state in melanoma. One hypothesis is that osmotic stress induces lncRNAs upregulation in these subpopulations, contributing to molecular crowding and driving liquid-liquid phase separation. The latter is a crucial physical process in signaling cascades and therefore could be responsible for several tumor phenotypes. It is thus interesting to characterize lncRNAs upregulated by osmotic stress, investigate their functions in melanoma and assess whether they can be used as therapeutic targets.