Oral communication, CS9 / C35

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

H19RNA downregulation in melasma

Recently, we reported that H19 downregulation might involve in melasma development, although the role in tumorigenesis but not in melanogenesis has been reported. Downregulation of the H19 gene was detected on microarray analysis of hyperpigmented and normally pigmented skin from melasma patients, and significant clinical correlations were identified. The H19 knockdown in melanocyte monoculture did not result in obvious tyrosinase overexpression, whereas the knockdown in a mixed normal human cell culture system, composed of H19 siRNA transfected keratinocytes and non-transfected melanocytes, did induce both a tyrosinase overexpression and an increase of melanosome transfer. Moreover, estrogen treatment of the H19 RNA knockdown in the mixed cell culture was more than an additive effect on the tyrosinase overexpression, whereas UV irradiation was not. Since H19RNA is a noncoding RNA, the importance could be determined with respect to the control of gene expression. Although the H19 consists of an imprinted cluster with IGF2, no reciprocal changes was detected between H19 and IGF2 RNA expression in the melasma. It has been reported that a 23-nucleotide microRNA, miR-675, derived from H19 is endogenously expressed in human keratinocytes. We found SUN3 as a target gene for miR-675. The SUN-3 expression was increased in the hyperpigmented compared to normally pigmented skin from melasma patients. The H19 knockdown using siRNA also increased the SUN3 expression, which involved in melanosome transfer. These findings supported the role H19 downregulation in the melasma development.

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