Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation.
Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation.
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差异表达lncRNA和circRNA的鉴定和整合分析揭示PDLSC成骨分化过程中潜在的ceRNA网络
DOI：
10.1186/s12863-017-0569-4
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发表时间：
2017-12-02
期刊：
影响因子：
2.9
通讯作者：
Wei F
中科院分区：
文献类型：
--
作者：
Gu X;Li M;Jin Y;Liu D;Wei F
研究人员一直在探索牙周膜干细胞（PDLSC）成骨分化的分子调控机制。最近，长链非编码RNA（lncRNA）和环状RNA（circRNA）被证明在细胞分化过程中作为竞争性内源RNA（ceRNA）来调节microRNA（miRNAs）对其靶基因的作用。然而，在PDLSC成骨分化期间充当ceRNA的lncRNA和circRNA的全面鉴定和整合分析尚未进行。PDLSCs来源于健康人牙周膜，分别在成骨诱导和正常培养基中培养7天。培养的PDLSC对STRO-1和CD 146呈阳性，对CD 31和CD 45呈阴性。成骨诱导的PDLSCs显示ALP（碱性磷酸酶）活性增加，成骨相关标志物ALP、Runt相关转录因子2和骨钙素的表达水平上调。然后，通过RNA测序发现总共960个lncRNA和1456个circRNA差异表达。8个lncRNA和8个circRNA的表达谱用定量实时聚合酶链反应测量，并显示与RNA-seq结果一致。此外，基于米兰达预测lncRNA和circRNA作为ceRNA的潜在功能，并使用基因本体论和京都基因和基因组百科全书分析进行研究。总共有147个lncRNA和1382个circRNA被预测与148个常见的miRNA联合收割机结合，并与744个信使RNA竞争miRNA结合位点。预计这些mRNA显着参与成骨细胞分化、MAPK途径、Wnt途径和调节干细胞多能性的信号途径。其中，编码TCONS_00212979和TCONS_00212984的lncRNA以及circRNA BANP和circRNA ITCH可能通过MAPK途径与miRNA 34 a和miRNA 146 a相互作用，调控PDLSC的成骨分化。本研究全面鉴定了lncRNA/circRNA，并首次整合了它们在PDLSC成骨分化过程中的潜在ceRNA功能。这些结果表明，特定的lncRNA和circRNA可能作为ceRNA的功能，以促进PDLSC成骨分化和牙周再生。本文的在线版本（10.1186/s12863-017-0569-4）包含补充材料，可供授权用户使用。
Researchers have been exploring the molecular mechanisms underlying the control of periodontal ligament stem cell (PDLSC) osteogenic differentiation. Recently, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were shown to function as competitive endogenous RNAs (ceRNAs) to regulate the effect of microRNAs (miRNAs) on their target genes during cell differentiation. However, comprehensive identification and integrated analysis of lncRNAs and circRNAs acting as ceRNAs during PDLSC osteogenic differentiation have not been performed. PDLSCs were derived from healthy human periodontal ligament and cultured separately with osteogenic induction and normal media for 7 days. Cultured PDLSCs were positive for STRO-1 and CD146 and negative for CD31 and CD45. Osteo-induced PDLSCs showed increased ALP (alkaline phosphatase) activity and up-regulated expression levels of the osteogenesis-related markers ALP, Runt-related transcription factor 2 and osteocalcin. Then, a total of 960 lncRNAs and 1456 circRNAs were found to be differentially expressed by RNA sequencing. The expression profiles of eight lncRNAs and eight circRNAs were measured with quantitative real-time polymerase chain reaction and were shown to agree with the RNA-seq results. Furthermore, the potential functions of lncRNAs and circRNAs as ceRNAs were predicted based on miRanda and were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. In total, 147 lncRNAs and 1382 circRNAs were predicted to combine with 148 common miRNAs and compete for miRNA binding sites with 744 messenger RNAs. These mRNAs were predicted to significantly participate in osteoblast differentiation, the MAPK pathway, the Wnt pathway and the signaling pathways regulating pluripotency of stem cells. Among them, lncRNAs coded as TCONS_00212979 and TCONS_00212984, as well as circRNA BANP and circRNA ITCH, might interact with miRNA34a and miRNA146a to regulate PDLSC osteogenic differentiation via the MAPK pathway. This study comprehensively identified lncRNAs/circRNAs and first integrated their potential ceRNA function during PDLSC osteogenic differentiation. These findings suggest that specific lncRNAs and circRNAs might function as ceRNAs to promote PDLSC osteogenic differentiation and periodontal regeneration. The online version of this article (10.1186/s12863-017-0569-4) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
2014-12
期刊：
RNA (New York, N.Y.)
影响因子：
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通讯作者：
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