Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi 710061, China.
Curr Gene Ther. 2019;19(5):305-317. doi: 10.2174/1566523219666191107113046.
Liver fibrosis or scarring is the most common pathological feature caused by chronic liver injury, and is widely considered one of the primary causes of morbidity and mortality. It is primarily characterised by hepatic stellate cells (HSC) activation and excessive extracellular matrix (ECM) protein deposition. Overwhelming evidence suggests that the dysregulation of several noncoding RNAs (ncRNAs), mainly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) contributes to the activation of HSC and progression of liver fibrosis. These ncRNAs not only bind to their target genes for the development and regression of liver fibrosis but also act as competing endogenous RNAs (ceRNAs) by sponging with miRNAs to form signaling cascades. Among these signaling cascades, lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA are critical modulators for the initiation, progression, and regression of liver fibrosis. Thus, targeting these interacting ncRNA cascades can serve as a novel and potential therapeutic target for inhibition of HSC activation and prevention and regression of liver fibrosis.
肝纤维化或瘢痕形成是慢性肝损伤最常见的病理特征,被广泛认为是发病率和死亡率的主要原因之一。其主要特征为肝星状细胞(HSC)激活和细胞外基质(ECM)蛋白过度沉积。大量证据表明,几种非编码 RNA(ncRNA)的失调,主要是长非编码 RNA(lncRNA)、微小 RNA(miRNA)和环状 RNA(circRNA),有助于 HSC 的激活和肝纤维化的进展。这些 ncRNA 不仅通过与靶基因结合来促进肝纤维化的发展和消退,还可以通过与 miRNA 结合形成信号级联反应作为竞争性内源 RNA(ceRNA)发挥作用。在这些信号级联反应中,lncRNA-miRNA-mRNA 和 circRNA-miRNA-mRNA 是肝纤维化起始、进展和消退的关键调节因子。因此,针对这些相互作用的 ncRNA 级联反应可以作为抑制 HSC 激活以及预防和逆转肝纤维化的一种新的潜在治疗靶点。