IL-33 is secreted by keratinocytes and functions as an alarmin. It may induce melanocyte death by regulating cytokines in the cellular microenvironment.

No abstract

The critical long non-coding RNAs (lncRNAs) involved in the carcinogenesis and progression of malignant melanoma (MM) have not been fully investigated. In the present study, it was identified that lncRNA activated by transforming growth factor-β (lncRNA-ATB) was upregulated in MM tissues and cells compared with benign nevus cells and human melanocytes, via comparative lncRNA screening from Gene Expression Omnibus datasets and reverse transcription-quantitative polymerase chain reaction analysis. Furthermore, lncRNA-ATB promoted the cell proliferation, cell migration, and cell invasion of MM cells in vitro, and tumor growth in vivo. It was additionally identified that lncRNA-ATB attenuated cell cycle arrest and inhibited cellular apoptosis in MM cells. Finally, it was demonstrated that lncRNA-ATB functions as a competing endogenous RNA (ceRNA) to enhance Yes associated protein 1 expression by competitively sponging microRNA miR-590-5p in MM cells. In conclusion, the present study revealed the expression and roles of lncRNA-ATB in MM, and indicated that lncRNA-ATB functions as a ceRNA to promote MM proliferation and invasion by sponging miR-590-5p.

Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable.

No abstract

Long intergenic noncoding RNA 00961 (Linc00961) has been identified as a tumor suppressor in various types of cancer. However, the critical roles of Linc00961 in the carcinogenesis and progression of skin melanoma (SM) are yet to be fully elucidated. The present study revealed via reverse transcription-quantitative PCR analysis that Linc00961 was downregulated in the tissues of patients with SM compared with benign nevi, and in A375, A2058 and SK-MEL-28 cell lines compared with human melanocytes. Furthermore, overexpression of Linc00961 inhibited cell proliferation, and promoted the apoptosis of A375 and SK-MEL-28 cells in vitro and in vivo , as determined by Cell Counting Kit-8 and flow cytometry assays, and tumor xenograft studies, respectively. Overexpression of Linc00961 also led to an attenuation of the migration and invasive capabilities of A375 and SK-MEL-28 cells, measured using Transwell assays. Functionally, it was demonstrated that Linc00961 acted as a competing endogenous RNA (ceRNA) by competitively sponging microRNA-367 (miR-367) in A375 and SK-MEL-28 cells; restoration of miR-367 rescued the inhibitory effects of Linc00961 on A375 and SK-MEL-28 cells. Finally, it was observed that phosphate and tension homology deleted on chromosome 10 (PTEN), an established target of miR-367 in A375 and SK-MEL-28 cells, was positively regulated by Linc00961, and its inhibition reversed the inhibitory effects of Linc00961 on the proliferation and invasion of A375 and SK-MEL-28 cells. Collectively, the present study revealed that Linc00961 was downregulated inSM, and furthermore, Linc00961 was identified as a ceRNA that inhibits the proliferation and invasion of A375 and SK-MEL-28 cells by modulating the miR-367/PTEN axis.

Oxidative stress leads to melanocyte death and has been implicated in the pathogenesis of vitiligo. The nuclear factor, E2‐related factor 2 (Nrf2), is a critical transcription factor in protecting cells from oxidative damage. High‐mobility group box 1 (HMGB1) is a chromatin‐associated nuclear protein and an extracellular damage‐associated molecular pattern molecule. Extracellular HMGB1 released from activated immune cells, necrotic or injured cells, becomes a proinflammatory mediator through binding to cell‐surface receptors of responding cells. In this study, we investigated the role of HMGB1 from melanocytes in the response to oxidative stress and the mechanism involved. We showed that HMGB1 is expressed by primary normal human epidermal melanocytes (NHEMs). H2O2 treatment increased cytoplasmic translocation and extracellular release of HMGB1. HMGB1 knockdown by small interfering RNA (siRNA) led to decreased apoptosis of NHEMs. HMGB1 inhibition enhanced the expression of Nrf2 and its target genes. The expression of Nrf2 and its downstream antioxidant genes was downregulated after the supernatant of H2O2‐treated NHEMs was added to HMGB1‐deficient cells. HMGB1 knockdown by siRNA suppressed the expression of the autophagosome marker, LC3, and enhanced p62 expression. Coimmunoprecipitation with Keap1 showed a reduced Nrf2‐Keap1 interaction and an increased p62‐Keap1 interaction under oxidative stress. These data demonstrated that external stimuli (eg, oxidative stress) may trigger autocrine HMGB1 translocation and release by melanocytes, suppressing the expression of Nrf2 and downstream antioxidant genes to induce melanocyte apoptosis, and thereby participate in the pathological process of vitiligo.

Oxidative stress serves a critical role in melanocyte death and is considered to be a major cause of vitiligo. The nuclear factor E2-related factor 2 (Nrf2) signaling pathway has an important role in the antioxidative stress mechanisms of melanocytes. Glycyrrhizin (GR) is a derivative of herbal medicines used to treat hepatitis and allergic disease due to its antiviral and anti-allergy effects. GR also activates Nrf2 and induces the expression of heme oxygenase (HO)-1 in macrophages. Whether GR can protect human melanocytes from oxidative stress remains unknown. The present study investigated the potential protective effects of GR against oxidative stress in human melanocytes and the mechanisms involved. Following exposure to 0.5 mM hydrogen peroxide (H 2 O 2 ), human primary melanocytes were treated with 1 mM GR. Cell viability was determined using a Cell Counting Kit-8 assay, and apoptosis was evaluated by flow cytometry. GR treatment significantly improved cell viability, reduced the apoptotic rate of melanocytes and reduced the level of reactive oxygen species in human melanocytes. Furthermore, GR induced the nuclear translocation of Nrf2 and induced the expression of HO-1 in melanocytes. The knockdown of Nrf2 by small interfering RNA or the inhibition of HO-1 by ZnPP reversed the protective effect of GR on melanocytes against H 2 O 2 -induced cytotoxicity and apoptosis. These data demonstrate that GR protects human melanocytes from H 2 O 2 -induced oxidative damage via the Nrf2-dependent induction of HO-1, providing evidence for the application of GR in the treatment of vitiligo.