A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway
A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway
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长非编码RNA HOTAIR通过抑制WIF-1表达和激活Wnt通路促进骨关节炎软骨退化
DOI：
10.1186/s12860-020-00299-6
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发表时间：
2020-06
影响因子：
2.8
通讯作者：
Li Jiao Jiao
中科院分区：
文献类型：
--
作者：
Yang Yang;Xing Dan;Wang Yawei;Jia Haobo;Li Bing;Li Jiao Jiao
研究背景长链非编码RNA（lncRNA）是近年来发现的表观基因组的重要调控因子。然而，我们对它们在骨关节炎（OA）发展中的作用的认识是有限的。本研究探讨了HOTAIR，一个关键的lncRNA与OA的表达升高，影响OA疾病progress.ResultsHOTAIR的表达大大升高，骨关节炎相比，正常软骨细胞的机制。HOTAIR在SW 1353细胞中的沉默和过表达分别减少和增加与OA中软骨降解相关的基因的表达。分子通路的研究表明，HOTAIR直接作用于Wnt抑制因子1（WIF-1），通过增加组蛋白H3 K27三甲基化的WIF-1启动子，导致WIF-1抑制，有利于激活的Wnt/β-catenin pathway.ConclusionsActivation Wnt/β-catenin signaling by HOTAIR through WIF-1 repression in ostearthritic chondrogenocytes增加分解代谢基因的表达，促进软骨降解。这是第一项证明HOTAIR，WIF-1和OA进展之间直接联系的研究，这可能有助于未来对疾病生物标志物或治疗靶点的研究。
BackgroundLong noncoding RNAs (lncRNAs) are recently found to be critical regulators of the epigenome. However, our knowledge of their role in osteoarthritis (OA) development is limited. This study investigates the mechanism by which HOTAIR, a key lncRNA with elevated expression in OA, affects OA disease progression.ResultsHOTAIR expression was greatly elevated in osteoarthritic compared to normal chondrocytes. Silencing and over-expression of HOTAIR in SW1353 cells respectively reduced and increased the expression of genes associated with cartilage degradation in OA. Investigation of molecular pathways revealed that HOTAIR acted directly on Wnt inhibitory factor 1 (WIF-1) by increasing histone H3K27 trimethylation in the WIF-1 promoter, leading to WIF-1 repression that favours activation of the Wnt/β-catenin pathway.ConclusionsActivation of Wnt/β-catenin signalling by HOTAIR through WIF-1 repression in osteoarthritic chondrocytes increases catabolic gene expression and promotes cartilage degradation. This is the first study to demonstrate a direct link between HOTAIR, WIF-1 and OA progression, which may be useful for future investigations into disease biomarkers or therapeutic targets.
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影响因子：
4.3
作者：
Hagen, Joshua W.;Lai, Eric C.
通讯作者：
Lai, Eric C.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbcan.2015.07.001
发表时间：
2015-08
期刊：
Biochimica et biophysica acta
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：
3.9
作者：
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通讯作者：
Harries, Lorna W.
影响因子：
12.7
作者：
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通讯作者：
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