Department of Prosthodontics, The First Affiliated Hospital of Xinjiang Medical University, Affiliated Stomatological Hospital of Xinjiang Medical University, Stomatology Research Institute of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China (mainland).
Department of Oral Implantology, The Affiliated Stomatology Hospital of Southwest Medical University; Orofacial Reconstruction and Regeneration Laboratory, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan, China (mainland).
Med Sci Monit. 2022 Jun 15;28:e936761. doi: 10.12659/MSM.936761.
BACKGROUND Circular RNAs (circRNAs) play important roles in gene expression and signaling pathways. The study aimed to identify the differential expression of circRNAs and mRNAs in the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and to explore the biological function of circRNAs in the osteogenic differentiation of rBMSCs. MATERIAL AND METHODS High-throughput sequencing was used to detect differentially expressed circular RNA and mRNA during osteogenic differentiation of rBMSCs. The RNAs were analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment to predict their potential role in regulating rBMSC osteogenesis. MiRanda, Circatlas, and miRDB databases were used to predict target relationships between circRNA, miRNA, and mRNA.The regulatory network was constructed by Cytoscape (version 3.6.1). The RNA-Seq findings were validated by quantitative real-time PCR (qRT-PCR). RESULTS The results revealed that 29 differentially expressed circRNAs and 2453 differentially expressed mRNAs were detected during the osteogenic differentiation of rBMSCs. Many differentially expressed circRNAs were closely related to osteogenic differentiation of cells. Among them, circRNAs_1809 and Kitlg were the significantly increased circRNA and mRNA during osteogenic differentiation of rBMSCs. The ceRNA network showed that circRNA_1809 could target the Kitlg gene through miR-370-3p. CONCLUSIONS CircRNAs may play an important role in the osteogenic differentiation of rBMSCs. CircRNA_1809 may acts as a sponge for miR-370-3p and regulate the osteogenic differentiation of rBMSCs by targeting Kitlg; however, this hypothesis needs further verification. This study laid a theoretical foundation for further understanding the mechanism of circRNAs regulating osteogenic differentiation of rBMSCs.
环状 RNA（circRNAs）在基因表达和信号通路中发挥重要作用。本研究旨在鉴定大鼠骨髓间充质干细胞（rBMSCs）成骨分化过程中差异表达的 circRNAs 和 mRNAs，并探讨 circRNAs 在 rBMSCs 成骨分化中的生物学功能。
采用高通量测序技术检测 rBMSCs 成骨分化过程中差异表达的 circRNA 和 mRNA。对 RNA 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，以预测其在调节 rBMSC 成骨中的潜在作用。利用 MiRanda、Circatlas 和 miRDB 数据库预测 circRNA、miRNA 和 mRNA 之间的靶标关系。通过 Cytoscape（版本 3.6.1）构建调控网络。采用实时荧光定量 PCR（qRT-PCR）验证 RNA-Seq 结果。
在 rBMSCs 成骨分化过程中，检测到 29 个差异表达的 circRNA 和 2453 个差异表达的 mRNA。许多差异表达的 circRNA 与细胞的成骨分化密切相关。其中，circRNAs_1809 和 Kitlg 在 rBMSCs 成骨分化过程中表达显著上调。ceRNA 网络显示，circRNA_1809 可通过 miR-370-3p 靶向 Kitlg 基因。
circRNAs 可能在 rBMSCs 的成骨分化中发挥重要作用。circRNA_1809 可能作为 miR-370-3p 的海绵分子，通过靶向 Kitlg 调节 rBMSCs 的成骨分化；然而，这一假设需要进一步验证。本研究为进一步了解 circRNAs 调节 rBMSCs 成骨分化的机制奠定了理论基础。
