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 Sirolimus during liver regeneration in vivo. Mechanistically, we discovered that lncRNA-LALR1 facilitated cyclin D1 expression through Bortezomib research buy 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. (Hepatology 2013;58:739–751) Liver regeneration is a series of physiopathological phenomena resulting in quantitative recovery from the loss of liver mass to compensate for decreased hepatic volume and impaired function.

Clinically, liver regeneration has important implications because many therapeutic strategies for the surgical treatment of liver diseases, such as removal of liver tumors and liver transplantation, depend on the ability of the liver to regenerate many physically and functionally. Insufficient liver regeneration may be potentially fatal for these patients.[1] Therefore, a better understanding of the mechanisms of liver regeneration could lead to clinical benefits. A complex network of cytokine and growth factor signaling involving molecules such as interleukin-6 (IL-6)[2] and hepatocyte growth factor (HGF)[3] regulates the hepatocyte cell cycle to ensure that liver regeneration occurs quickly.[4] Recent studies have shown the critical role of microRNAs (miRNAs), such as miR-221[5] and miR-21,[6] in liver regeneration. Although various cytokines, growth factors, and miRNAs have been shown to regulate genes that orchestrate proliferation during liver regeneration, new molecular therapeutic targets for liver failure and liver transplantation are still urgently needed. It is important to understand the overall molecular changes that occur during liver regeneration to enhance the effectiveness of current regenerative technology.