LB1004 miR-4521 is over-expressed in human lentigos and downregulates components of the autophagic pathway in keratinocytes

Lentigo is a common cutaneous pigmented lesion associated with age and sun exposure where keratinocytes demonstrate increased melanin pigmentation. Prior studies have been investigated the molecular pathogenesis of lentigos; however, mechanisms leading to lentigo formation remain poorly understood. As first step in exploring pathogenesis, we performed laser-capture microdissection human tissue sections capturing lesional epidermis from five patients three matched control skin samples. Total RNA was isolated these dissected tissues then pooled into ‘lentigo’ ‘epidermal’ These samples were analyzed on an Affymetrix GeneChip® Human Gene 2.0 ST array for gene expression profiling. A total 1777 genes differentially expressed at least 1.8-fold FDR < 0.1. One transcript miR-4521 which found be 38.31 fold higher lentigos. Additional showed that mir-4521 levels 17-fold lentigos (N=5) compared subjects (N=3) by qRT-PCR (p<0.05) further confirmed situ hybridization showing keratinocytes. In silico analysis indicated targets GABARAPL2 other autophagy. Downregulation both mRNA protein using microRNA precursor transfection experiments HaCaT cells. Immunohistochemistry positive staining upper layers lentigos, contrast basal layer unremarkable epidermis. data indicate it may regulate autophagic pathway