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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-Catenin signaling
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Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-Catenin signaling

机译：与肝再生有关的长非编码RNA 1通过激活Wnt /β-Catenin信号传导，在肝再生期间加速肝细胞增殖

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摘要

In recent years, long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of biological function. A recent study reported that lncRNAs control cell proliferation in hepatocellular carcinoma (HCC). However, the role of lncRNAs in liver regeneration and the overall mechanisms remain largely unknown. To address this issue, we carried out a genome-wide lncRNA microarray analysis during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various timepoints. The results revealed differential expression of a subset of lncRNAs, notably a specific differentially expressed lncRNA associated with Wnt/β-catenin signaling during liver regeneration (an lncRNA associated with liver regeneration, termed lncRNA-LALR1). The functions of lncRNA-LALR1 were assessed by silencing and overexpressing this lncRNA in vitro and in vivo. We found that lncRNA-LALR1 enhanced hepatocyte proliferation by promoting progression of the cell cycle in vitro. Furthermore, we showed that lncRNA-LALR1 accelerated mouse hepatocyte proliferation and cell cycle progression during liver regeneration in vivo. Mechanistically, we discovered that lncRNA-LALR1 facilitated cyclin D1 expression through activation of Wnt/β-catenin signaling by way of suppression of Axin1. In addition, lncRNA-LALR1 inhibited the expression of Axin1 mainly by recruiting CTCF to the AXIN1 promoter region. We also identified a human ortholog RNA of lncRNA-LALR1 (lncRNA-hLALR1) and found that it was expressed in human liver tissues. Conclusion: lncRNA-LALR1 promotes cell cycle progression and accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-catenin signaling. Pharmacological intervention targeting lncRNA-LALR1 may be therapeutically beneficial in liver failure and liver transplantation by inducing liver regeneration.
机译：近年来，长的非编码RNA（lncRNA）已被研究作为一种新型的生物功能调节剂。最近的研究报道，lncRNAs控制肝细胞癌（HCC）中的细胞增殖。然而，lncRNAs在肝再生中的作用和整体机制仍是未知之数。为了解决这个问题，我们在2/3部分肝切除术（PH）后的不同时间点，在小鼠肝脏再生期间进行了全基因组的lncRNA微阵列分析。结果揭示了lncRNA的子集的差异表达，特别是在肝再生期间与Wnt /β-catenin信号传导相关的特异性差异表达的lncRNA（与肝再生相关的lncRNA，称为lncRNA-LALR1）。通过在体外和体内沉默和过表达该lncRNA来评估lncRNA-LALR1的功能。我们发现lncRNA-LALR1通过促进体外细胞周期的进展来增强肝细胞增殖。此外，我们表明，lncRNA-LALR1在体内肝脏再生过程中可加速小鼠肝细胞增殖和细胞周期进程。从机制上，我们发现lncRNA-LALR1通过抑制Axin1激活Wnt /β-catenin信号传导来促进cyclin D1表达。另外，lncRNA-LALR1主要通过将CTCF募集到AXIN1启动子区域来抑制Axin1的表达。我们还鉴定了lncRNA-LALR1（lncRNA-hLALR1）的人类直系同源RNA，并发现它在人类肝脏组织中表达。结论：lncRNA-LALR1通过激活Wnt /β-catenin信号传导促进肝再生过程中的细胞周期进程并加速肝细胞增殖。靶向lncRNA-LALR1的药理干预可能通过诱导肝再生而在肝衰竭和肝移植中具有治疗优势。

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