Ming Guang-Fu, Gao Bo-Hua, Chen Peng
Department of Orthopedics, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Evol Bioinform Online. 2021 Oct 21;17:11769343211041379. doi: 10.1177/11769343211041379. eCollection 2021.
The etiology of osteosarcoma (OS) is complex and not fully understood till now. This study aimed to identify the miRNAs, circRNAs, and genes (mRNAs) that are differentially expressed in OS cell lines to investigate the mechanism of circRNA-associated competing endogenous RNAs (ceRNAs) in OS. Microarray datasets reporting mRNA (GSE70414), miRNA (GSE70367), and circRNA changes (GSE96964) in human OS cell lines were downloaded, differentially expressed (DE) RNAs were identified, and DEmRNAs were used for the annotation of Gene Ontology (GO) biological processes (BP), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The mechanisms of DEcircRNA-mediated ceRNAs were identified in a step-by-step process. A total of 326 DEmRNAs, 45 DEmiRNAs, and 110 DEcircRNAs were identified from 3 datasets. The DEmRNAs were associated with GO BP terms, including cholesterol biosynthetic process, angiogenesis, extracellular matrix organization and KEGG pathways, including p53 signaling pathway and biosynthesis of antibiotics. The final ceRNA network consisted of 8 DEcircRNAs, including 5 pappalysin (PAPPA) 1-derived DEcircRNAs (hsa_circ_0005456, hsa_circ_0088209, hsa_circ_0002052, hsa_circ_0088214 and has_circ_0008792, all downregulated), 3 DEmiRNAs (hsa-miR-760, hsa-miR-4665-5p and hsa-miR-4539, all upregulated), and downregulated genes (including MMP13 and HMOX1). The ceRNA regulation network of OS was built, which played important roles in the pathogenesis of OS and might be of great importance in therapy.
骨肉瘤（OS）的病因复杂，至今尚未完全明确。本研究旨在鉴定在OS细胞系中差异表达的微小RNA（miRNA）、环状RNA（circRNA）和基因（mRNA），以探究circRNA相关的竞争性内源RNA（ceRNA）在OS中的作用机制。下载了报告人类OS细胞系中mRNA（GSE70414）、miRNA（GSE70367）和circRNA变化（GSE96964）的微阵列数据集，鉴定差异表达（DE）RNA，并将DEmRNA用于基因本体论（GO）生物学过程（BP）注释以及京都基因与基因组百科全书（KEGG）通路分析。逐步鉴定DEcircRNA介导的ceRNA机制。从3个数据集中共鉴定出326个DEmRNA、45个DEmiRNA和110个DEcircRNA。DEmRNA与GO BP术语相关，包括胆固醇生物合成过程、血管生成、细胞外基质组织，以及KEGG通路，包括p53信号通路和抗生素生物合成。最终的ceRNA网络由8个DEcircRNA组成，包括5个源自妊娠相关血浆蛋白A（PAPPA）1的DEcircRNA（hsa_circ_0005456、hsa_circ_0088209、hsa_circ_0002052、hsa_circ_0088214和has_circ_0008792，均下调）、3个DEmiRNA（hsa-miR-760、hsa-miR-4665-5p和hsa-miR-4539，均上调）以及下调基因（包括基质金属蛋白酶13（MMP13）和血红素加氧酶1（HMOX1））。构建了OS的ceRNA调控网络，其在OS发病机制中起重要作用，可能对治疗具有重要意义。
