Comprehensive analysis of long noncoding RNAs and mRNAs expression profiles and functional networks during chondrogenic differentiation of murine ATDC5 cells
Comprehensive analysis of long noncoding RNAs and mRNAs expression profiles and functional networks during chondrogenic differentiation of murine ATDC5 cells
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小鼠 ATDC5 细胞软骨分化过程中长非编码 RNA 和 mRNA 表达谱和功能网络的综合分析
DOI：
10.1093/abbs/gmz064
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发表时间：
2019
影响因子：
3.7
通讯作者：
Li Song
中科院分区：
文献类型：
--
作者：
Wang Wei;Ding Yu;Xu Yanhua;Yang Hefeng;Liu Wenjing;Wang Haixia;Chen Ceshi;Liu Rong;Li Song
软骨形成分化是由各种细胞信号通路协调的协调生物过程，涉及在转录和转录后水平上调节的复杂通路。长非编码 RNA (lncRNA) 正在成为调节多种细胞过程的重要调节因子。然而，lncRNA 的潜在作用及其在软骨分化中的调节机制仍不清楚。本研究采用微阵列技术检测小鼠软骨细胞系 ATDC5 软骨形成过程中 lncRNA 和信使 RNA (mRNA) 的表达谱。通过基因本体论（GO）和京都基因和基因组百科全书（KEGG）途径分析来探索它们的功能。还利用生物信息学方法构建了编码-非编码共表达（CNC）和竞争性内源RNA（ceRNA）网络。结果显示，1009 个 lncRNA 和 1206 个 mRNA 在软骨分化过程中受到差异调节。 GO和KEGG通路分析表明转录本的主要功能与系统发育和细胞外基质-受体相互作用、TGF-β信号传导和PI3K-Akt信号通路相关。 CNC网络显示lncRNA AK136902与前列腺素F受体（FP）呈正相关。 ceRNA网络覆盖3个lncRNA、121个miRNA和241条边。上调的lncRNA AK136902、AK016344和ENSMUST00000180767可能通过充当ceRNA来促进软骨形成分化。敲低lncRNA AK136902可抑制软骨分化过程中FP和其他软骨形成相关基因（包括Aggrecan和Col2a1）的mRNA表达。我们的结果为软骨分化过程中 lncRNA 的调节提供了新的视角。
Chondrogenic differentiation is a coordinated biological process orchestrated by various cell signaling pathways, involving complex pathways regulated at both transcriptional and post-transcriptional levels. Long noncoding RNAs (lncRNAs) are emerging as important regulators in the modulation of multiple cell processes. However, the potential roles of lncRNAs and their regulatory mechanisms in chondrogenic differentiation remain largely unclear. In this study, microarray was performed to detect the expression profiles of lncRNAs and messenger RNAs (mRNAs) during chondrogenic differentiation of murine chondrogenic cell line ATDC5. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore their functions. Coding-noncoding co-expression (CNC) and competing endogenous RNA (ceRNA) networks were also constructed with bioinformatics methods. The results revealed that 1009 lncRNAs and 1206 mRNAs were differentially regulated during chondrogenic differentiation. GO and KEGG pathway analysis indicated that the principal functions of the transcripts were associated with system development and extracellular matrix-receptor interaction, TGF-β signaling, and PI3K-Akt signaling pathways. The CNC network showed that lncRNA AK136902 was positively correlated with prostaglandin F receptor (FP). The ceRNA network covered 3 lncRNAs, 121 miRNAs and 241 edges. The upregulated lncRNA AK136902, AK016344, and ENSMUST00000180767 might promote chondrogenic differentiation by acting as ceRNAs. Knockdown of lncRNA AK136902 could inhibit the mRNA expression of FP and other chondrogenic related genes, includingAggrecanandCol2a1during chondrogenic differentiation. Our results provide a new perspective on the modulation of lncRNAs during chondrogenic differentiation.