PDF(Pubmed)
Abstract：
Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve as an activated HSCs regulator via regulating NF2 and Hippo pathway.
摘要：
长非编码RNA小核仁RNA宿主基因5（SNHG5）是在各种人类癌症中发现的癌基因。然而,目前尚不清楚SNHG5在激活肝星状细胞（HSC）和肝纤维化中的作用。在这项研究中,发现SNHG5在体外活化的HSC和体内从纤维化肝分离的原代HSC中上调，SNHG5的抑制抑制了HSC的活化。值得注意的是,神经纤维蛋白2（NF2），河马信号的主要激活器，参与SNHG5对HSC激活的影响。进一步证实了SNHG5与NF2蛋白之间的相互作用,阻止两者的联合使用可以有效阻断SNHG5抑制对EMT过程和Hippo信号传导的影响。此外,在慢性乙型肝炎患者中发现较高的SNHG5，并与纤维化阶段相关。总之,我们证明SNHG5可以通过调节NF2和Hippo途径作为激活的HSC调节因子。
