Identification of miR-145 as a Key Regulator of the Pigmentary Process

Abstract

The current treatments for hyperpigmentation are often associated with a lack of efficacy and adverse side effects. We hypothesized that microRNA (miRNA)-based treatments may offer an attractive alternative by specifically targeting key genes in melanogenesis. The aim of this study was to identify miRNAs interfering with the pigmentary process and to assess their functional role. miRNA profiling was performed on mouse melanocytes after three consecutive treatments involving forskolin and solar-simulated UV (ssUV) irradiation. Sixteen miRNAs were identified as differentially expressed in treated melan-a cells versus untreated cells. Remarkably, a 15-fold downregulation of miR-145 was detected. Overexpression or downregulation of miR-145 in melan-a cells revealed reduced or increased expression of Sox9, Mitf, Tyr, Trp1, Myo5a, Rab27a, and Fscn1, respectively. Moreover, a luciferase reporter assay demonstrated direct targeting of Myo5a by miR-145 in mouse and human melanocytes. Immunofluorescence tagging of melanosomes in miR-145-transfected human melanocytes displayed perinuclear accumulation of melanosomes with additional hypopigmentation of harvested cell pellets. In conclusion, this study has established an miRNA signature associated with forskolin and ssUV treatment. The significant down- or upregulation of major pigmentation genes, after modulating miR-145 expression, suggests a key role for miR-145 in regulating melanogenesis.

MicroRNA-processing Enzymes Are Essential for Survival and Function of Mature Retinal Pigmented Epithelial Cells in Mice

“…Thus, it is possible that loss of miRNAs in melanocytes could cause pigmentary changes resulting in alterations in coat color. Indeed, several melanocyte miRNAs are linked to either melanocyte survival or pigmentation processes (47)(48)(49)(50)(51). Therefore, we hypothesized that the link between coat color and the severity of retinal degeneration might arise from Cre expression patterns that vary from animal to animal but remain consistent within the pigmentary cells of the same animal.…”

DermaGene and VitmiRS: a comprehensive systems analysis of genetic dermatological disorders

“…SIRT1 has been shown to regulate stress-activated MAPK pathway via Akt and ASK1 in vitiligo keratinocytes (Becatti et al 2014). Previous studies have demonstrated the influence of miR-145 on the genes involved in the pigmentation process (Dynoodt et al 2013). The genes targeted by miR-145 also regulate MAPK pathway along with JNK and TGFB signaling pathway and are related to the functional groups that might indirectly influence cellular processes in vitiligo wherefore they interfere with melanocytes function and viability (Šahmatova et al 2016) suggesting the role of both miR-9 and miR-145 in the destruction of melanocytes in vitiligo.…”

MicroRNA-218 inhibits melanogenesis by directly suppressing microphthalmia-associated transcription factor expression

“…A total of 2.88 × 10 5 human infected melanocytes were seeded onto each dermal layer for 24 h and 7.2 × 10 5 HaCaT cells were seeded onto the melanocytes to construct the epidermis. The OTC was cultured for 2 d and then raised to the air-liquid interface.…”

“…4 A recent study also reported that miR-145 regulates depigmentary activity through the suppression of MYO5A expression in mouse and human melanocytes. 5 As a critical transcriptional factor, MITF knockout affects many miRNAs expression profiles in melanocytes. 6 Therefore, the identification of MITF-targeted melanogenic miRNAs should give insight into the regulatory mechanisms of melanogenesis and provide new promising targets for depigmentation.…”