title: Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo.
abstract: Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo.
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: Q
authors: Q
authors: Shi
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: W
authors: W
authors: Zhang
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: S
authors: S
authors: Guo
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: Z
authors: Z
authors: Jian
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: S
authors: S
authors: Li
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: K
authors: K
authors: Li
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: R
authors: R
authors: Ge
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: W
authors: W
authors: Dai
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: G
authors: G
authors: Wang
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: T
authors: T
authors: Gao
authors: Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shannxi, China.
authors: C
authors: C
authors: Li
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000502:physiology*; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D034622:RNA Interference; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism; D014820:Vitiligo / Q000097:blood* / Q000235:genetics / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C543351:MIRN25 microRNA, human; C497234:MITF protein, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; D019089:Stem Cell Factor; D016222:Fibroblast Growth Factor 2