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蕈样肉芽肿的进展可能受到 microRNAs 的调控。

Mycosis fungoides progression could be regulated by microRNAs.

机构信息

Pathology Department, Fundación Jiménez Díaz, UAM, Madrid, CIBERONC, Madrid, Spain.

Laboratorio de Genómica del Cáncer, IDIVAL, Fundación Marques de Valdecilla, Santander, Spain.

出版信息

PLoS One. 2018 Jun 12;13(6):e0198477. doi: 10.1371/journal.pone.0198477. eCollection 2018.

Abstract

Differentiating early mycosis fungoides (MF) from inflammatory dermatitis is a challenge. We compare the differential expression profile of early-stage MF samples and benign inflammatory dermatoses using microRNA (miRNA) arrays. 114 miRNAs were found to be dysregulated between these entities. The seven most differentially expressed miRNAs between these two conditions were further analyzed using RT-PCR in two series comprising 38 samples of early MFs and 18 samples of inflammatory dermatitis. A series of 51 paraffin-embedded samples belonging to paired stages of 16 MF patients was also analyzed. MiRNAs 26a, 222, 181a and 146a were differentially expressed between tumoral and inflammatory conditions. Two of these miRNAs (miRNA-181a and miRNA-146a) were significantly deregulated between early and advanced MF stages. Bioinformatic analysis showed FOXP3 expression to be regulated by these miRNAs. Immunohistochemistry revealed the level of FOXP3 expression to be lower in tumoral MFs than in plaque lesions in paraffin-embedded tissue. A functional study confirmed that both miRNAs diminished FOXP3 expression when overexpressed in CTCL cells. The data presented here suggest that the analysis of a restricted number of miRNAs (26a, 222, 181a and 146a) could be sufficient to differentiate tumoral from reactive conditions. Moreover, these miRNAs seem to be involved in MF progression.

摘要

早期蕈样肉芽肿(MF)与炎症性皮肤病的鉴别具有挑战性。我们使用 microRNA(miRNA)阵列比较了早期 MF 样本和良性炎症性皮肤病的差异表达谱。发现这两种实体之间有 114 个 miRNA 失调。在两个包含 38 个早期 MF 样本和 18 个炎症性皮肤病样本的系列中,进一步使用 RT-PCR 分析了这两种状态之间差异表达最明显的七个 miRNA。还分析了来自 16 个 MF 患者配对阶段的一系列 51 个石蜡包埋样本。miRNA-26a、222、181a 和 146a 在肿瘤和炎症条件之间表达不同。这两个 miRNA(miRNA-181a 和 miRNA-146a)在早期和晚期 MF 阶段之间存在显著失调。生物信息学分析显示 FOXP3 的表达受这些 miRNA 调控。免疫组织化学显示,在石蜡包埋组织中,肿瘤性 MF 中的 FOXP3 表达水平低于斑块病变。功能研究证实,当在 CTCL 细胞中过表达时,这两个 miRNA 均降低了 FOXP3 的表达。这里提出的数据表明,对少数 miRNA(26a、222、181a 和 146a)的分析可能足以区分肿瘤性和反应性疾病。此外,这些 miRNA 似乎参与了 MF 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0fc/5997347/8040b3cff06a/pone.0198477.g001.jpg

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