Detection and Analysis of the Hedgehog Signaling Pathway-Related Long Non-Coding RNA (IncRNAs) Expression Profiles in Keloid
Detection and Analysis of the Hedgehog Signaling Pathway-Related Long Non-Coding RNA (IncRNAs) Expression Profiles in Keloid
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DOI：
10.12659/msm.911159
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发表时间：
2018-12-13
影响因子：
3.1
通讯作者：
Liu, Dewu
中科院分区：
文献类型：
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作者：
Huang, Heping;Fu, Shangfeng;Liu, Dewu
背景：Hhedgehog(HH)信号通路相关基因在涉及细胞增殖的多种生理和疾病过程中发挥重要作用。长非编码区RNA(IncRNAs)对基因表达具有调节作用。瘢痕疙瘩的特点是创伤后瘢痕组织过度增殖。本研究的目的是研究HH信号通路在瘢痕疙瘩组织及其下游基因表达和IncRNAs中的表达，并与正常皮肤进行比较。材料/方法：提取4对瘢痕疙瘩及其邻近正常皮肤表皮的总RNA。应用基因芯片高通量实时定量聚合酶链式反应(QPCR)检测HH信号通路相关的IncRNAs和mRNAs在人瘢痕疙瘩和正常皮肤中的差异表达。用基因本体论(GO)和京都基因与基因组百科全书(KEGG)对差异表达的mRNAs进行分析。结果：基因芯片定量聚合酶链式反应证实了瘢痕疙瘩组织中与HH途径相关的33个mRNAs和30个IncRNAs的差异表达。GO和KEGG分析结果表明，上调的mRNAs参与细胞的增殖、生长和组织修复，下调的mRNAs参与细胞凋亡。IncRNA AC073257.2通过其上游的GLI2基因在转录水平上影响瘢痕疙瘩细胞的生长和增殖。IncRNA HNF1A-AS1通过其邻近的靶基因HNF1A影响瘢痕疙瘩细胞的生长和增殖。结论：HH信号通路相关的IncRNAs和mRNAs在瘢痕疙瘩中存在差异表达，为进一步了解瘢痕疙瘩的发生发展提供了可能。
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 (IncRNAs) 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 IncRNAs, compared with normal skin.Material/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 IncRNAs 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 IncRNAs 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 IncRNA, AC073257.2, affected cell keloid growth and proliferation by its upstream target the GLI2 gene at the transcriptional level. The IncRNA, HNF1A-AS1, affected cell keloid growth and proliferation by its neighboring target gene, HNF1A.Conclusions: Differential expression occurred in Hh signaling pathway-related IncRNAs and mRNAs, which may provide further insight into the development of keloid.