LncRNA HOTTIP enhances human osteogenic BMSCs differentiation via interaction with WDR5 and activation of Wnt/β-catenin signalling pathway
LncRNA HOTTIP enhances human osteogenic BMSCs differentiation via interaction with WDR5 and activation of Wnt/β-catenin signalling pathway
复制标题
LncRNA HOTTIP 通过与 WDR5 相互作用并激活 Wnt/β-catenin 信号通路增强人成骨 BMSC 分化
DOI：
10.1016/j.bbrc.2020.02.034
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发表时间：
2020-04-16
影响因子：
3.1
通讯作者：
Jin, Anmin
中科院分区：
文献类型：
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作者：
Liu, Ruiduan;Li, Zihao;Jin, Anmin
为了揭示长非编码RNA在骨髓间充质干细胞(BMSCs)成骨分化过程中的分子机制，采用LncRNA微阵列技术筛选了HoxA基因末端转录本。结果表明，在人骨髓间充质干细胞成骨分化过程中，热休克蛋白表达显著上调。ShRNA下调热休克蛋白表达可抑制骨髓间充质干细胞的成骨分化。慢病毒载体过表达热休克蛋白可促进人骨髓间充质干细胞的成骨分化，促进β-连环蛋白的转录。RIP实验和RNA下拉实验证实了HotIP与与β-连环蛋白启动子结合的转录因子WDR5的相互作用。这种相互作用促进了WDR5的核内转位，并增加了β-连环蛋白的转录。移植热休克蛋白过表达的BMSCs可增加裸鼠异位成骨。HotTip是一种保守的长非编码RNA，对骨髓间充质干细胞的成骨分化是必不可少的。HotTip通过与WDR5相互作用，上调β-catenin基因表达，从而激活Wnt/β-catenin信号通路，从而促进成骨分化。(C)2020 Elsevier Inc.保留所有权利。
To uncover the underlying molecular mechanism of long non-coding RNA in the osteogenic differentiation process of bone marrow mesenchymal stem cells (BMSCs), HOXA transcript at the distal tip (HOTTIP) was selected by using a lncRNA microarray assay. Results showed that HOTTIP was significantly upregulated during osteogenic differentiation of human BMSCs. Downregulation of HOTTIP by shRNA inhibited the osteogenic differentiation of BMSCs. Overexpression of HOTTIP by lentiviral vector promoted human BMSCs osteogenic differentiation by increasing the transcription of beta-catenin. RIP assay and RNA pulldown assay confirmed the interaction between HOTTIP and WDR5, a transcription factor binding to the promoter of beta-catenin. The interaction promoted the translocation of WDR5 into the nucleus and increased the transcription of beta-catenin. Implanted HOTTIP-overexpressing BMSCs increased ectopic bone formation in nude mice. HOTTIP is a conservative long noncoding RNA that is essential for osteogenic differentiation of BMSC. HOTTIP enhances osteogenic differentiation via interaction with WDR5 and up-regulation of beta-catenin gene expression, therefore activating Wnt/beta-catenin signalling pathway. (C) 2020 Elsevier Inc. All rights reserved.