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长非编码 RNA 表现出差异表达谱,并在胆脂瘤发病机制中显示 ceRNA 潜能。

Long noncoding RNAs show differential expression profiles and display ceRNA potential in cholesteatoma pathogenesis.

机构信息

Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

Center of Excellence in Tissue Engineering, Key Laboratory of Beijing, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China.

出版信息

Oncol Rep. 2018 May;39(5):2091-2100. doi: 10.3892/or.2018.6320. Epub 2018 Mar 16.

Abstract

Cholesteatoma is a pathologically benign but clinically destructive middle ear disease, which is caused by excessive epidermal migration and uncontrolled hyperproliferation of keratinocytes of squamous epithelium, leading to various clinical manifestations and serious complications, such as hearing loss, dizziness, facial paralysis, meningitis, and hydrocephalus. However, the pathogenesis of cholesteatoma is still not fully understood. Herein, we performed microarray analysis to identify the differentially expressed patterns of lncRNAs in cholesteatoma for the first time. Our data indicated that compared with matched normal skin tissue, lncRNA expression profiles were significantly altered in cholesteatoma. A total of 787 lncRNAs were identified (fold change ≥2.0, P<0.05), consisting of 181 upregulated and 606 downregulated lncRNAs. Furthermore, by constructing an lncRNA/miRNA/mRNA competing endogenous RNA (ceRNA) network, we found that lncRNAs, such as lncRNA‑uc001kfc.1, had ceRNA potential in cholesteatoma formation. In conclusion, lncRNAs were aberrantly expressed in cholesteatoma compared with normal skin tissues and may play important roles in cholesteatoma formation. Our findings shed novel light on the molecular mechanism of cholesteatoma pathogenesis and suggest that lncRNAs may be potential therapeutic targets for cholesteatoma.

摘要

胆脂瘤是一种病理良性但临床破坏性的中耳疾病,由鳞状上皮的角质形成细胞过度迁移和不受控制的过度增殖引起,导致各种临床表现和严重并发症,如听力损失、头晕、面瘫、脑膜炎和脑积水。然而,胆脂瘤的发病机制仍不完全清楚。在此,我们首次进行了微阵列分析,以鉴定胆脂瘤中差异表达的 lncRNA 模式。我们的数据表明,与匹配的正常皮肤组织相比,胆脂瘤中的 lncRNA 表达谱明显改变。总共鉴定出 787 个 lncRNA(倍数变化≥2.0,P<0.05),包括 181 个上调和 606 个下调的 lncRNA。此外,通过构建 lncRNA/miRNA/mRNA 竞争内源 RNA(ceRNA)网络,我们发现 lncRNA-uc001kfc.1 等 lncRNA 在胆脂瘤形成中具有 ceRNA 潜能。总之,与正常皮肤组织相比,lncRNA 在胆脂瘤中表达异常,可能在胆脂瘤形成中发挥重要作用。我们的研究结果为胆脂瘤发病机制的分子机制提供了新的见解,并表明 lncRNA 可能是胆脂瘤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/833f/5928766/ddc340c80740/OR-39-05-2091-g00.jpg

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