miR-146a Exerts Differential Effects on Melanoma Growth and Metastatization

摘要: Malignant melanoma is the most aggressive form of skin cancer; therefore, it crucial to disclose its underlying molecular mechanisms. MicroRNAs (miRNAs) are small endogenous noncoding RNAs able posttranscriptionally downregulate expression direct target genes. Using a progression model, miR-146a was identified as key double-acting player in malignancy. In fact, enhance tumor growth, while suppresses dissemination. It determined that coordinated cell growth by targets lunatic fringe (LFNG) and NUMB, which operate on NOTCH/PTEN/Akt pathway; inhibition metastasis formation linked decreased ITGAV ROCK1. Relevantly, correlated with recurrence enriched both patient-derived cutaneous specimens, were depleted. However, levels drop circulating cells (CTCs), suggesting necessity for fluctuate during order favor allow This study reconciles contradictory biologic functions unravels distinct mechanisms need be considered therapeutic interventions. Implications: controls dual way, promoting inhibiting dissemination; however, poorly expressed CTCs, resulting overall spreading distant-site colonization. Mol Cancer Res; 14(6); 548–62. ©2016 AACR .