Yao Tao, Yin Zong-Sheng, Huang Wei, Ding Zhen-Fei, Cheng Chao
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University.
Department of Orthopaedics, The First People's Hospital of Hefei, the Third Affiliated Hospital of Anhui Medical University.
Medicine (Baltimore). 2020 Mar;99(10):e19465. doi: 10.1097/MD.0000000000019465.
The aim of this study was to elucidate the molecular mechanisms and to identify the differential expression of circular RNAs (circRNAs) for steroid-associated osteonecrosis of the femoral head (SONFH) using bioinformatics analysis.circRNA microarray was performed with 3 SONFH tissues and the adjacent normal tissues, and differentially expressed circRNA were identified by limma package in R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. In addition, a differentially expressed genes (DEG)-associated circRNA/microRNA (miRNA) interaction was predicted by combination of TargetScan and miRanda, and the circRNA/miRNA interaction network generated by the cytoscape software.A total of 647 differentially expressed circRNAs, including 433 upregulated and 214 downregulated circRNA were identified. The most enriched GO terms for upregulated and downregulated circRNA were extracellular matrix organization and leukocyte activation in biological process; extracellular matrix and spindle pole in cellular component; integrin binding and ATP binding in molecular function, and KEGG pathway enrichment analyses showed that the upregulated and downregulated circRNA were strongly associated with Protein digestion and absorption and Cell cycle. Moreover, a total of 212 differentially expressed messenger RNAs (mRNAs), including 113 upregulated and 99 downregulated genes were identified. In addition, from the analysis of miRNA, long noncoding RNAs, mRNA, and circRNA networks, we found that hsa_circ_0008136 and hsa_circ_0074758 were respectively the upregulated and downregulated circRNA with highest degrees.The identified circRNA and mRNA could be implicated in the progression of human SONFH. The findings could lead to a better understanding of SONFH pathogenesis.
本研究旨在通过生物信息学分析阐明类固醇相关的股骨头坏死（SONFH）的分子机制并鉴定环状RNA（circRNA）的差异表达。对3个SONFH组织及其相邻正常组织进行circRNA微阵列分析，并使用R语言中的limma软件包鉴定差异表达的circRNA。利用注释、可视化与集成发现数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。此外，通过TargetScan和miRanda相结合预测差异表达基因（DEG）相关的circRNA/微小RNA（miRNA）相互作用，并利用Cytoscape软件生成circRNA/miRNA相互作用网络。共鉴定出647个差异表达的circRNA，其中包括433个上调的和214个下调的circRNA。上调和下调circRNA最丰富的GO术语在生物学过程中分别为细胞外基质组织和白细胞活化；在细胞成分中为细胞外基质和纺锤体极；在分子功能中为整合素结合和ATP结合，KEGG通路富集分析表明上调和下调的circRNA与蛋白质消化和吸收以及细胞周期密切相关。此外，共鉴定出212个差异表达的信使RNA（mRNA），其中包括113个上调的和99个下调的基因。此外，通过对miRNA、长链非编码RNA、mRNA和circRNA网络的分析，我们发现hsa_circ_0008136和hsa_circ_0074758分别是上调和下调程度最高的circRNA。所鉴定的circRNA和mRNA可能与人类SONFH的进展有关。这些发现有助于更好地理解SONFH的发病机制。
