The long non-coding RNA ANRIL, antisense to the CDKN2B locus, is transcribed from a gene that encompasses multiple disease-associated polymorphisms.,Despite the identification of multiple isoforms of ANRIL, expression of certain transcripts has been found to be tissue-specific and the characterisation of ANRIL transcripts remains incomplete.,Several functions have been associated with ANRIL.,In our judgement, studies on ANRIL functionality are premature pending a more complete appreciation of the profusion of isoforms.,We found differential expression of ANRIL exons, which indicates that multiple isoforms exist in melanoma cells.,In addition to linear isoforms, we identified circular forms of ANRIL (circANRIL).,Further characterisation of circANRIL in two patient-derived metastatic melanoma cell lines (NZM7 and NZM37) revealed the existence of a rich assortment of circular isoforms.,Moreover, in the two melanoma cell lines investigated, the complements of circANRIL isoforms were almost completely different.,Novel exons were also discovered.,We also found the family of linear ANRIL was enriched in the nucleus, whilst the circular isoforms were enriched in the cytoplasm and they differed markedly in stability.,With respect to the variable processing of circANRIL species, bioinformatic analysis indicated that intronic Arthrobacter luteus (Alu) restriction endonuclease inverted repeats and exon skipping were not involved in selection of back-spliced exon junctions.,Based on our findings, we hypothesise that “ANRIL” has wholly distinct dual sets of functions in melanoma.,This reveals the dynamic nature of the locus and constitutes a basis for investigating the functions of ANRIL in melanoma.
In the present study, we analyzed the role of microRNA-194 circulating regulated human melanoma cell growth.,We found that microRNA-194 expression was markedly suppressed in human melanoma patients, compared with negative control group.,Next, disease-free survival (DFS) and overall survival (OS) of high expression in human melanoma patients was higher than those of low expression in human melanoma patients.,MicroRNA-194 overexpression inhibited cell proliferation, induced apoptosis, increased caspase-3/−9 activities and promoted Bax/Bcl-2 of human melanoma cells.,Furthermore, microRNA-194 overexpression also suppressed PI3K/AKT/FoxO3a signaling pathway and induced p53/p21 signaling pathway.,PI3K inhibitor, suppressed PI3K, phosphorylation-AKT, FoxO3a protein expression and increased the effects of microRNA-194 overexpression on cell growth, apoptosis, caspase-3/−9 activities and Bax/Bcl-2 protein expression of human melanoma cells through the induction of p53/p21 signaling pathway.,Taken together, these data indicate that circulating microRNA-194 regulated human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway.