MicroRNA-21 regulates the ERK/NF-κB signaling pathway to affect the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN.

This study aims to explore the effects of microRNA-21 (miR-21) and ERK/NF-κB signaling pathway on human melanoma A375 cells. The melanoma tissues and adjacent normal tissues were obtained from 45 melanoma patients. qRT-PCR was conducted to quantify the expression of miR-21 and the gene mRNA expressions. Human melanoma A375 cells were divided into the Mock, negative control (NC), miR-21 inhibitors, miR-21 inhibitors + siRNA-SPRY1, miR-21 inhibitors + siRNA-PDCD4, and miR-21 inhibitors + siRNA-PTEN groups. Western blotting was used to determine protein expressions. CCK8 assay and Transwell assay were performed to evaluate the proliferation, migration, and invasion of A375 cells. Annexin V/propidium iodide double staining was adopted to detect cell apoptosis. MiR-21 expression was higher in melanoma tissues than in adjacent tissues, while the mRNA and protein expressions of SPRY1, PDCD4, and PTEN were lower in melanoma tissues than in adjacent tissues. Compared with the Mock and NC groups, the miR-21 inhibitors group exhibited increased expressions of SPRY1, PDCD4, and PTEN and decreased expressions of ERK, p-ERK, NF-κB p65, and p-NF-κB p65. After transfection of miR-21 inhibitors, the proliferation, migration, and invasion of A375 cells were inhibited, while the apoptosis of A375 cells was promoted. However, the effects of miR-21 inhibitors on the growth, migration, invasion, and apoptosis of A375 cells were reversed after transfection of siRNA-SPRY1, siRNA-PDCD4, or siRNA-PTEN. MiR-21 can promote the proliferation, migration, and inhibit the apoptosis of human melanoma A375 cells by inhibiting SPRY1, PDCD4, and PTEN via ERK/NF-κB signaling pathway. © 2016 Wiley Periodicals, Inc.

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial.

Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.

[The methylation locus and frequency pattern on p16 INK4a gene promoter CpG in epidermis of patients with psoriasis].

OBJECTIVE: To investigate the CpG methylation locus and frequency pattern on p16 INK4a gene promoter in epidermis of p16 INK4a methylated patients with psoriasis vulgaris. METHODS: The DNA specimens were obtained from epidermal lesion of 50 plaque psoriatic patients. Methylation specific PCR and DNA sequencing were used to detect the frequency and locus of methylation in p16 INK4a gene promoter region. RESULTS: Approximately 50% CpG was methylated in p16 INK4a methylated patients, methylation was found in specifical locus of p16 INK4a gene promoter. CONCLUSION: The distinct methylation pattern is showed on the p16 INK4a gene promoter region in patients with psoriasis.

Two new mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. Genetic studies have identified mutations in ADAR1 gene to be responsible for this disorder. We detected two mutations in two families with DSH, which include a heterozygous g-->a transversion at the first base of the 3'-acceptor splice site of intron 5 (c. 2080-1g>a, IVS5-1g>a) and a transition c.3076C>T. IVS5-1g>a should prevent proper splicing of the transcript while c.3076C>T leading to a missense mutation p.R1026W of the ADAR1 gene. Our study suggests that splice site mutation IVS5-1g>a and missense mutation p.R1026W are new mutations of ADAR1 gene, which should be useful in genetic counseling and prenatal diagnosis for the affected families and expanding the database on ADAR1 gene mutations in DSH.