Transcriptomic profiling and functional prediction reveal aberrant expression of circular RNAs during osteogenic differentiation in human umbilical cord mesenchymal stromal cells.
Transcriptomic profiling and functional prediction reveal aberrant expression of circular RNAs during osteogenic differentiation in human umbilical cord mesenchymal stromal cells.
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转录组分析和功能预测揭示人脐带间充质基质细胞成骨分化过程中环状RNA的异常表达
DOI：
10.1038/s41598-021-98470-2
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发表时间：
2021-10-06
影响因子：
4.6
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Su C;Zheng X;He Y;Long L;Chen W
环状 RNA (circRNA) 是非编码 RNA 的关键元件，调节各种生物过程。迄今为止，circRNA在人脐带间充质基质细胞（hUCMSC）成骨分化过程中的表达模式和功能作用仍然未知。在这项研究中，我们分析了 RNA 序列数据，揭示了 hUCMSC 成骨过程中 circRNA 的表达谱，然后阐明了潜在的作用机制。我们在 hUCMSC 中总共鉴定了 5457 个 circRNA，其中 34 个和 33 个分别上调和下调。我们应用基因本体论和京都基因和基因组百科全书分析来确定差异表达的 circRNA 的功能和相关途径。此外，我们应用生物信息学工具构建了竞争性内源RNA网络，包括10个circRNA、46个micro RNA和413个mRNA。此外，我们预测了上调的 circRNA 的蛋白质编码潜力，然后构建了一个包含前 5 个上调的 circRNA 和 75 个 RNA 结合蛋白的共表达网络。接下来，我们验证了 6 个差异表达的 circRNA，发现过表达 circ-CTTN 可以促进 hUCMSC 的成骨。总的来说，我们的研究结果表明，在成骨分化过程中，circRNA簇在hUCMSCs中异常表达，因此为未来促进hUCMSCs成骨分化和骨再生的研究奠定了基础。
Circular RNAs (circRNAs) are crucial elements of non-coding RNA, that regulate various biological processes. To date, expression patterns and functional roles of circRNAs during osteogenic differentiation of human umbilical cord mesenchymal stromal cells (hUCMSCs) remain unknown. In this study, we analyzed RNA-sequence data to reveal expression profiles of circRNAs during osteogenesis of hUCMSCs, then elucidated the underlying mechanisms of action. We identified a total of 5457 circRNAs in hUCMSCs, of which 34 and 33 were upregulated and downregulated, respectively. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine functions and related pathways of differentially expressed circRNAs. Moreover, we applied bioinformatics tools to construct competing endogenous RNA networks, comprising 10 circRNAs, 46 micro RNAs and 413 mRNAs. Furthermore, we predicted protein-coding potential of the upregulated circRNAs then constructed a co-expression network comprising the top 5 upregulated circRNAs and 75 RNA-binding proteins. Next, we validated 6 differentially-expressed circRNAs and found that overexpressing circ‐CTTN could promote osteogenesis of hUCMSCs. Overall, our findings indicate that clusters of circRNAs are aberrantly expressed in hUCMSCs during osteogenic differentiation, hence lay a foundation for future research into promoting hUCMSCs osteogenic differentiation and bone regeneration.
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