Dataset Information

Role of the p53?TRPM1/miR?211?MMP9 axis in UVB?induced human melanocyte migration and its potential in repigmentation.

ABSTRACT: Clinical studies have proven that ultraviolet B (UVB) based phototherapy can induce perifollicular and marginal repigmentation patterns in the skin of vitiligo patients. It is, however, difficult to conceive how melanocytes can easily exit from their tightly interconnected epidermal microenvironment to re?enter a different location in the skin to establish a new network with neighboring keratinocytes. While it is known that matrix metalloprotease 9 (MMP9) is involved in the degradation of the extracellular matrix in physiological or pathological processes, little is known about whether MMP9 affects melanocyte migration in vitiligo repigmentation. To investigate the effects of the p53? transient receptor potential cation channel subfamily M member 1 (TRPM1)/microRNA (miR/miRNA)?211?MMP9 axis to regulate melanocyte migration following exposure to UVB, the expression profile of MMP9 in cultured human melanocytes transfected with or without the miR?211?mimic and p53?GFP lentiviral vector, respectively were determined. Quantitative polymerase chain reaction and western blotting were used to examine p53, TRPM1 and MMP9 mRNA and protein levels in UVB?exposed and unexposed cells. The capacity of melanocytes to migrate on collagen IV substrate was estimated using a Transwell migration assay. Interestingly, the upregulation of p53 and MMP9 at the mRNA and protein levels was evident in melanocytes treated with single or repeat exposures to UVB, whereas levels of TRPM1 and miR?211 were significantly suppressed in UVB?exposed melanocytes compared with the UVB?unexposed control cells. These results indicate that the p53?TRPM1/miR?211?MMP9 axis is significantly activated in melanocytes exposed to UVB. Notably, the ability of melanocyte migration was altered by the overexpression of p53 using a lentiviral vector and by the upregulation of miR?211 using an miRNA mimic. That altered migration could be neutralized by co?treatment with GM6001 (a broad?spectrum MMP inhibitor). Overall, these results show that the MMP9?mediated migration of melanocytes is regulated by a novel mechanism driven by the p53?TRPM1/miR?211?MMP9 axis. Activation of the p53?TRPM1/miR?211?MMP9 axis potentially represents an attractive therapeutic target to improve repigmentation outcomes in vitiligo patients.

SUBMITTER: Su M

PROVIDER: S-EPMC7053874 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Role of the p53‑TRPM1/miR‑211‑MMP9 axis in UVB‑induced human melanocyte migration and its potential in repigmentation.

Su Mengyun M Miao Fang F Jiang Shan S Shi Ying Y Luo Longfei L He Xiaolei X Wan Jing J Xu Shizheng S Lei Tie-Chi TC

International journal of molecular medicine 20200127 4

Clinical studies have proven that ultraviolet B (UVB) based phototherapy can induce perifollicular and marginal repigmentation patterns in the skin of vitiligo patients. It is, however, difficult to conceive how melanocytes can easily exit from their tightly interconnected epidermal microenvironment to re‑enter a different location in the skin to establish a new network with neighboring keratinocytes. While it is known that matrix metalloprotease 9 (MMP9) is involved in the degradation of the ex ...[more]

PMID: 31985026

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Project description:ObjectiveIn the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion.MethodsExpression profiles of EC miRNAs and matched clinical data were accessed from TCGA database for differential and survival analyses. Bioinformatics databases were employed to predict the downstream targets of the potential miRNA, and enrichment analysis was performed on the miRNA and corresponding target gene using GSEA software. qRT-PCR was conducted to detect the expression levels of miR-29c-3p and CCNA2 mRNA in EC tissues and cells, and Western blot was performed for the examination of CCNA2, CDK1 and p53 protein levels. Subsequently, cells were harvested for MTT, Transwell as well as flow cytometry assays to examine cell viability, migration, invasion and cell cycle. Dual-luciferase reporter gene assay and RIP were carried out to further investigate and verify the targeted relationship between miR-29c-3p and CCNA2.ResultsMiR-29c-3p was shown to be significantly down-regulated in EC tissues and able to predict poor prognosis. CCNA2 was found to be a downstream target of miR-29c-3p and mainly enriched in cell cycle and p53 signaling pathway, whereas miR-29c-3p was remarkably activated in cell cycle. MiR-29c-3p overexpression inhibited cell proliferation, migration and invasion, as well as arrested cells in G0/G1 phase. As suggested by dual-luciferase reporter gene assay and RIP, CCNA2 was under the regulation of miR-29c-3p, and the negative correlation between the two genes was verified. Silencing CCNA2 could suppress cell proliferation, migration and invasion, as well as activate p53 pathway, even was seen to reverse the inhibitory effect of PFTβ on p53. Besides, in the presence of low miR-29c-3p, CCNA2 was up-regulated while p53 was simultaneously inhibited, resulting in the promotion of cell migration, invasion and cell cycle arrest.ConclusionMiR-29c-3p plays a regulatory role in EC tumorigenesis and development. MiR-29c-3p can target CCNA2 to mediate p53 signaling pathway, finally attributing to the inhibition of cell proliferation, migration and invasion, and making cells arrest in G0/G1 phase.

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Dataset Information

Role of the p53?TRPM1/miR?211?MMP9 axis in UVB?induced human melanocyte migration and its potential in repigmentation.

Publications

Role of the p53‑TRPM1/miR‑211‑MMP9 axis in UVB‑induced human melanocyte migration and its potential in repigmentation.

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