Transcriptome stability profiling identifies novel and functional MIRNA targets in melanoma cells

Melanoma has a high propensity to metastasize and is often lethal. Effective biomarkers and therapies are lacking, so candidate identification remains a clinical priority. RNA half-life is closely related to its cellular physiological function, and stability determinants may therefore have regulatory functions. Micro(MI)RNAs have primarily been studied with respect to post-transcriptional mRNA regulation and target degradation. Here we study the impact of tumor suppressive melanoma MIRNA MIR211 on transcriptome stability and phenotype in the A375 amelanotic melanomacell line. Using 5-bromouridineIP chase ( BRIC)-seq, transcriptome-wide RNA stability profiles revealed highly regulated genes and pathways important in this melanoma cell line. Using a combinatorial approach of BRIC-seq, RNA-seq, and in silicopredictions, we identify both existing and novel direct MIR211 targets. DUSP3 is validated as one such novel MIR211 target, which itself sustains colony formation and invasion in A375 cells, probably via MAPK/PI3K signaling. MIRNAs have the capacity to control RNA turnover as a gene expression mechanism. RNA stability profiling is an excellent tool for interrogating functionally relevant cancer pathways and MIRNA targets when combined with other high-throughput and in silicoapproaches.