MicroRNA-340 is involved in ultraviolet B-induced pigmentation by regulating the MITF/TYRP1 axis

Abstract

Objective There is growing evidence that ultraviolet B (UVB) irradiation can change the expression profile of microRNAs (miRNAs) in immortalized human epidermal melanocytes (Pig-1). We aimed to investigate the effect of miR-340 on regulating UVB-induced pigmentation. Methods Real-time quantitative PCR (qRT-PCR) was used to evaluate the expression of miR-340 in Pig-1 cells. Immunoblotting analysis, qRT-PCR, and luciferase reporter assays were used to detect the potential target of miR-340. The sodium hydroxide dissolution assay was used to assess the effect of miR-340 on changes in melanin content. Results Expression of miR-340 was reduced in human Pig-1 cells after UVB irradiation. We found a negative correlation between miR-340 and melanocyte inducing transcription factor (MITF) in Pig-1 cells after UVB irradiation. Knockdown and overexpression of MITF in Pig-1 cells down- and upregulated melanogenesis, respectively. Overexpression of miR-340 inhibited MITF expression, reduced the amount of melanin, and suppressed expression of multiple key molecules involved in the pigment synthesis pathway, whereas knockdown of miR-340 showed the opposite results. Conclusions Our results showed that miR-340 inhibited melanogenesis by regulating the downstream molecules of MITF and its signaling pathways, suggested that miRNA-340 may be a new target for the clinical treatment of UVB-induced pigmentation.

microRNAs in the Regulation of Melanogenesis

“…Overall, most identified miRNAs, including miR-25, miR508-3p, miR-137, miR-218, miR-183, miR-340, miR-141-3p, and miR-200a-3p, target MITF , leading to a decrease in its gene expression and consequent melanogenesis inhibition [ 52 , 58 , 61 , 62 , 63 , 73 ]. These miRNAs include miR-137, which was able to modulate coat color in transgenic mice [ 57 ].…”

“…The miR-183 cluster was also involved in regulating the MEK/ERK signaling pathway implicated in cell proliferation and migration, by modulating mitogen-activated protein kinase 1 (MEK1), extracellular regulated protein kinases1/2 (ERK1/2), and CREB expression [ 62 ]. miR-340, which was first identified in melanoma cell lines for its ability to bind specifically to the 3′-UTR of MITF [ 64 ], has been also investigated in immortalized human epidermal melanocytes (Pig-1), where it downregulates MITF expression and melanin synthesis [ 63 ]. Recently, miR-141-3p and miR-200a-3p have been identified as MITF regulators [ 52 ].…”

“…Recently, the functional role of miR-340 has been further investigated in immortalized human epidermal melanocytes (Pig-1), confirming that its expression is modulated by UV and that it downregulates MITF expression and melanin synthesis. Notably, miR-340 mimics decreased melanin content in irradiated cells [ 63 ]. A further example of a miR potentially being involved in UV-induced pigmentation modulation is miR-21.…”

Silencing of Rab23 by siRNA inhibits ultraviolet B‐induced melanogenesis via downregulation of PKA / CREB / MITF

“…During this process, Rab27a, myosin Va and melanophilin (Mlph) form a tripartite protein complex involved in the transportation of melanosomes from microtubules to actin fibres 10,11 . Moreover, the extension of dendrites may be required for the transportation of melanosomes to the dendrite tip 9,12,13 …”

“…10,11 Moreover, the extension of dendrites may be required for the transportation of melanosomes to the dendrite tip. 9,12,13 Rab23 is a conserved member of the Rab family of small GTPases found in various organisms, ranging from yeast to humans, and are involved in membrane assembly and docking between specific vesicles and organelles in eukaryotic cells. 14 Reportedly, Rab GTPases, such as Rab27a, Rab6, Rab7 and Rab32/38, can regulate melanosomal logistics by sorting and transporting cargo proteins, including melanogenic enzymes, into immature melanosomes, and subsequent transportation of melanosomes through interactions with cellular motors.…”