Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts.
Comprehensive Analysis of Circular RNA Expression in ceRNA Networks and Identification of the Effects of hsa_circ_0006867 in Keloid Dermal Fibroblasts.
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ceRNA网络中环状RNA表达的综合分析及hsa_circ_0006867在瘢痕疙瘩真皮成纤维细胞中的作用鉴定
DOI：
10.3389/fmolb.2022.800122
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发表时间：
2022
影响因子：
5
通讯作者：
Xu J
中科院分区：
文献类型：
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作者：
Pang Q;Lin X;Sun J;Hu J;Dai S;Shen Y;Xu M;Xu J
环状rna （circRNAs）在各种纤维化疾病的发病机制中起着至关重要的作用，但环状rna在瘢痕疙瘩中的潜在生物学功能和表达谱尚不清楚。本研究采用微阵列技术检测了四种患者源性瘢痕疙瘩真皮成纤维细胞（KDFs）和正常真皮成纤维细胞（ndf）中的circRNA表达。共鉴定出327个差异表达（DE）环状rna (fold change bbb1.5, p < 0.05)，其中195个表达上调，132个表达下调。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析显示，上调的环状rna主要富集于细胞骨架和紧密连接，而下调的环状rna则与上皮和轴突引导的形态发生有关。为了探索DE circrna的功能，利用生物信息学分析构建了一个circRNA-miRNA-mRNA网络，包括5个circrna， 9个mirna和235个相关mrna。通过qRT-PCR在18对kdf和ndf中验证了5种DE circRNAs的表达，hsa_circ_0006867在体外瘢痕疙瘩中显示出有希望的调节功能。沉默hsa_circ_00006867可抑制瘢痕疙瘩成纤维细胞的增殖、迁移和侵袭。rna结合蛋白免疫沉淀（RIP）实验表明，hsa_circ_00006867可能作为miRNA结合Argonaute (AGO) 2的平台。此外，hsa-miR-29a-5p可能是hsa_circ_00006867的潜在靶标miRNA。综上所述，我们的研究为了解瘢痕疙瘩的病理生理机制提供了多种新的线索，并确定了hsa_circ_0006867作为瘢痕疙瘩的生物标志物。
Circular RNAs (circRNAs) play a crucial role in the pathogenesis of various fibrotic diseases, but the potential biological function and expression profile of circRNAs in keloids remain unknown. Herein, microarray technology was applied to detect circRNA expression in four patient-derived keloid dermal fibroblasts (KDFs) and normal dermal fibroblasts (NDFs). A total of 327 differentially expressed (DE) circRNAs (fold change > 1.5, p < 0.05) were identified with 195 upregulated and 132 downregulated circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the upregulated circRNAs were mainly enriched in the cytoskeleton and tight junctions, while the downregulated circRNAs were related to morphogenesis of the epithelium and axonal guidance. To explore the function of DE circRNAs, a circRNA-miRNA-mRNA network, including five circRNAs, nine miRNAs, and 235 correlated mRNAs, was constructed using bioinformatics analyses. The expression of five DE circRNAs was validated by qRT–PCR in 18 pairs of KDFs and NDFs, and hsa_circ_0006867 showed promising regulatory function in keloids in vitro. Silencing hsa_circ_00006867 suppressed the proliferation, migration, and invasion of keloid fibroblasts. RNA-binding protein immunoprecipitation (RIP) assays indicated that hsa_circ_00006867 may serve as a platform for miRNA binding to Argonaute (AGO) 2. In addition, hsa-miR-29a-5p may be a potential target miRNA of hsa_circ_00006867. Taken together, our research provided multiple novel clues to understand the pathophysiologic mechanism of keloids and identified hsa_circ_0006867 as a biomarker of keloids.
核Argonaute-sal-sal-all RNA复合物和治疗途径的各种作用。
DOI：
10.1038/mtna.2014.54
发表时间：
2014-10-14
期刊：
Molecular therapy. Nucleic acids
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