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蛋白激酶 C 抑制剂作用下人角质形成细胞差异表达 microRNA 谱

Differential miRNA expression profiles in human keratinocytes in response to protein kinase C inhibitor.

机构信息

Burns Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):6608-6619. doi: 10.3892/mmr.2017.7447. Epub 2017 Sep 8.

DOI:10.3892/mmr.2017.7447
PMID:28901412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5865793/
Abstract

Aberrant expression of microRNAs (miRNAs) is widely accepted to be involved in keratinocyte differentiation and to be dependent on activation of the protein kinase C (PKC) pathway. However, the miRNA profiles and biological characteristics of keratinocytes induced by specific inhibitors of PKC have yet to be elucidated. The present study aimed to explore the differential miRNA expression profiles in keratinocytes treated with the PKC inhibitor GF109203X, by conducting a bioinformatics analysis. Parts of the GF109203X‑induced keratinocytes formed distinct clones after 2 days of culture, and the expression of intergrin β1, cytokeratin (CK)19 and CK14 were positive, whereas CK10 expression was negative. A total of 79 miRNAs were differentially expressed in keratinocytes treated with GF109203X, among which 45 miRNAs were upregulated and 34 were downregulated. The significantly upregulated microRNAs includedhsa‑miR‑1‑3p and miR‑181c‑5p, whereas hsa‑miR‑31‑5p and hsa‑let‑7c‑3p were significantly downregulated. In addition, the results of reverse transcription‑quantitative polymerase chain reaction exhibited consistency with the microarray results. An enrichment analysis demonstrated that certain target genes of the differentially expressed miRNAs serve an important role in cell proliferation and differentiation, cell cycle progression and apoptosis, etc. These results revealed that GF109203X induced the differential expression of certain miRNAs when keratinocytes began showing the characteristics of epidermal‑like stem cells, which may provide a novel approach for wound healing and regeneration of skin tissues.

摘要

异常表达的 microRNAs(miRNAs)被广泛认为参与角质形成细胞分化,并依赖于蛋白激酶 C(PKC)途径的激活。然而,PKC 特定抑制剂诱导的角质形成细胞的 miRNA 谱和生物学特征尚未阐明。本研究旨在通过生物信息学分析探讨 PKC 抑制剂 GF109203X 处理角质形成细胞后的差异 miRNA 表达谱。部分 GF109203X 诱导的角质形成细胞在培养 2 天后形成明显的克隆,整合素β1、细胞角蛋白(CK)19 和 CK14 的表达为阳性,而 CK10 的表达为阴性。GF109203X 处理的角质形成细胞中有 79 个 miRNA 表达差异,其中 45 个 miRNA 上调,34 个 miRNA 下调。显著上调的 microRNAs 包括 hsa-miR-1-3p 和 miR-181c-5p,而 hsa-miR-31-5p 和 hsa-let-7c-3p 则显著下调。此外,逆转录-定量聚合酶链反应的结果与微阵列结果一致。富集分析表明,差异表达 miRNA 的某些靶基因在细胞增殖和分化、细胞周期进程和细胞凋亡等方面发挥着重要作用。这些结果表明,GF109203X 诱导角质形成细胞开始表现出表皮样干细胞特征时,某些 miRNA 的差异表达,这可能为皮肤组织的创伤愈合和再生提供一种新的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317f/5865793/6d5f1c779eb6/mmr-16-05-6608-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317f/5865793/0585830b215f/mmr-16-05-6608-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317f/5865793/6d5f1c779eb6/mmr-16-05-6608-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317f/5865793/0585830b215f/mmr-16-05-6608-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317f/5865793/6d5f1c779eb6/mmr-16-05-6608-g01.jpg

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