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瘢痕疙瘩中 Hedgehog 信号通路相关长链非编码 RNA(lncRNA)表达谱的检测与分析。

Detection and Analysis of the Hedgehog Signaling Pathway-Related Long Non-Coding RNA (lncRNA) Expression Profiles in Keloid.

机构信息

Institute of Burns, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland).

Department of Plastic and Aesthetic Surgery, Jingxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China (mainland).

出版信息

Med Sci Monit. 2018 Dec 13;24:9032-9044. doi: 10.12659/MSM.911159.

Abstract

BACKGROUND Hedgehog (Hh) signaling pathway-related genes have important roles in several physiological and disease processes that involve cell proliferation. Long non-coding region RNAs (lncRNAs) have a regulatory role on gene expression. Keloid is characterized by excessive proliferation of scar tissue following trauma. The aims of this study were to evaluate the Hh signaling pathway in keloid skin tissues and its downstream gene expression and lncRNAs, compared with normal skin. MATERIAL AND METHODS Four pairs of keloids and adjacent normal skin epidermis underwent total RNA extraction. Gene chip high-throughput real-time quantitative polymerase chain reaction (qPCR) was used to examine the differential expression profiles of the Hh signaling pathway-related lncRNAs and mRNAs in the human keloid and normal skin. The differentially expressed mRNAs were analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify their biological roles. RESULTS In keloid tissue, differential expression of 33 mRNAs and 30 lncRNAs relating to the Hh pathway, were verified by gene chip qPCR. The results of GO and KEGG analysis showed that the upregulated mRNAs were involved in cell proliferation, cell growth, and tissue repair, and down-regulated mRNAs were involved in apoptosis. The lncRNA, AC073257.2, affected cell keloid growth and proliferation by its upstream target the GLI2 gene at the transcriptional level. The lncRNA, HNF1A-AS1, affected cell keloid growth and proliferation by its neighboring target gene, HNF1A. CONCLUSIONS Differential expression occurred in Hh signaling pathway-related lncRNAs and mRNAs, which may provide further insight into the development of keloid.

摘要

背景

Hedgehog(Hh)信号通路相关基因在涉及细胞增殖的几个生理和疾病过程中具有重要作用。长链非编码 RNA(lncRNA)在基因表达中具有调节作用。瘢痕疙瘩是指创伤后瘢痕组织过度增殖。本研究旨在评估瘢痕疙瘩皮肤组织中的 Hh 信号通路及其下游基因表达和 lncRNA,与正常皮肤进行比较。

材料和方法

4 对瘢痕疙瘩和相邻正常皮肤表皮进行总 RNA 提取。采用基因芯片高通量实时定量聚合酶链反应(qPCR)检测 Hh 信号通路相关 lncRNA 和 mRNA 在人瘢痕疙瘩和正常皮肤中的差异表达谱。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析差异表达的 mRNAs,以确定其生物学作用。

结果

通过基因芯片 qPCR 验证了 33 个与 Hh 通路相关的 mRNAs 和 30 个 lncRNAs 在瘢痕疙瘩组织中的差异表达。GO 和 KEGG 分析结果表明,上调的 mRNAs 参与细胞增殖、细胞生长和组织修复,而下调的 mRNAs 参与细胞凋亡。lncRNA AC073257.2 通过其上游靶基因 GLI2 基因在转录水平上影响细胞瘢痕生长和增殖。lncRNA HNF1A-AS1 通过其邻近靶基因 HNF1A 影响细胞瘢痕生长和增殖。

结论

Hh 信号通路相关 lncRNA 和 mRNAs 的差异表达可能为瘢痕疙瘩的发生发展提供进一步的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ee9/6301256/4b8f0207424a/medscimonit-24-9032-g001.jpg

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