Department of Stomatology of Maoming People's Hospital, Maoming, 525000, China.
Department of Stomatology of Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
BMC Genomics. 2022 Jan 3;23(1):1. doi: 10.1186/s12864-021-08243-4.
The mechanism implicated in the osteogenesis of human periodontal ligament stem cells (PDLSCs) has been investigated for years. Previous genomics data analyses showed that long noncoding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) have significant expression differences between induced and control human PDLSCs. Competing for endogenous RNAs (ceRNA), as a widely studied mechanism in regenerative medicine, while rarely reported in periodontal regeneration. The key lncRNAs and their ceRNA network might provide new insights into molecular therapies of periodontal regeneration based on PDLSCs.
Two networks reflecting the relationships among differentially expressed RNAs were constructed. One ceRNA network was composed of 6 upregulated lncRNAs, 280 upregulated mRNAs, and 18 downregulated miRNAs. The other network contained 33 downregulated lncRNAs, 73 downregulated mRNAs, and 5 upregulated miRNAs. Functional analysis revealed that 38 GO terms and 8 pathways related with osteogenesis were enriched. Twenty-four osteogenesis-related gene-centred lncRNA-associated ceRNA networks were successfully constructed. Among these pathways, we highlighted MAPK and TGF-beta pathways that are closely related to osteogenesis. Subsequently, subnetworks potentially linking the GO:0001649 (osteoblast differentiation), MAPK and TGF-beta pathways were constructed. The qRT-PCR validation results were consistent with the microarray analysis.
We construct a comprehensively identified lncRNA-associated ceRNA network might be involved in the osteogenesis of PDLSCs, which could provide insights into the regulatory mechanisms and treatment targets of periodontal regeneration.
人类牙周膜干细胞（PDLSCs）成骨的机制已经研究了多年。先前的基因组数据分析表明，诱导和对照人牙周膜干细胞之间长非编码 RNA（lncRNA）、微小 RNA（miRNA）和信使 RNA（mRNA）的表达存在显著差异。竞争内源性 RNA（ceRNA）作为再生医学中广泛研究的机制，在牙周再生中很少报道。关键的 lncRNA 及其 ceRNA 网络可能为基于 PDLSCs 的牙周再生的分子治疗提供新的见解。
构建了两个反映差异表达 RNA 之间关系的网络。一个 ceRNA 网络由 6 个上调的 lncRNA、280 个上调的 mRNA 和 18 个下调的 miRNA 组成。另一个网络包含 33 个下调的 lncRNA、73 个下调的 mRNA 和 5 个上调的 miRNA。功能分析显示，有 38 个与成骨相关的 GO 术语和 8 个途径被富集。成功构建了 24 个与成骨相关的基因中心 lncRNA 相关的 ceRNA 网络。在这些途径中，我们突出了与成骨密切相关的 MAPK 和 TGF-β途径。随后，构建了潜在连接 GO：0001649（成骨细胞分化）、MAPK 和 TGF-β途径的子网络。qRT-PCR 验证结果与微阵列分析一致。
我们构建了一个全面鉴定的 lncRNA 相关 ceRNA 网络，可能参与 PDLSCs 的成骨作用，为牙周再生的调控机制和治疗靶点提供了新的见解。
