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Long non-coding RNAs (lncRNAs) have been reported to be involved in many important biological processes including proliferation, apoptosis, differentiation, and survival. Recently, nuclear paraspeckle assembly transcript 1 (NEAT1), a novel lncRNA, serves as a crucial regulator in tumors. However, the biological role of NEAT1 in liver fibrosis is largely unknown. In this study, the role of NEAT1 was explored in primary mouse hepatic stellate cells (HSCs) and carbon tetrachloride (CCl)-induced mouse liver fibrosis models. We found that NEAT1 expression was significantly increased in CCl-induced mice and activated HSCs. Loss of NEAT1 suppressed liver fibrosis in vivo and in vitro. Conversely, NEAT1 overexpression accelerated HSC activation, including increased cell proliferation and collagen expression. Further studies indicated that the microRNA-122 (miR-122)-Kruppel-like factor 6 (KLF6) axis was involved in the effects of NEAT1 on HSC activation. The effects of NEAT1 on HSC activation were almost blocked down by miR-122 mimics or KLF6 knockdown. Interestingly, both NEAT1 and KLF6 are targets of miR-122. In addition, miR-122 led to a significant reduction in NEAT1 level while NEAT1 overexpression resulted in the suppression of miR-122 expression. Pull-down assay confirmed a direct interaction between miR-122 and NEAT1. NEAT1 contributes to HSC activation via the miR-122-KLF6 axis. In human fibrotic liver samples, increased NEAT1 levels positively correlated with liver fibrosis markers. In conclusion, we disclose a novel NEAT1-miR-122-KLF6 signaling cascade and its implication in liver fibrosis. Key messages: [ABSTRACT FROM AUTHOR]

Background: Previously, we reported that microRNA-181b (miR-181b) activates hepatic stellate cells partly through the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/Akt pathway. Aims: The main objective of this study was to ascertain whether serum miR-181b expression is correlated with that of liver hepatitis B virus (HBV) DNA and disease progression in chronic hepatitis B (CHB) patients. Methods: Serum miR-181b and liver HBV DNA levels were quantified in 64 CHB patients with real-time PCR. Liver fibrosis and necroinflammation were graded according to the Ishak scoring system. Results: Serum miR-181b levels were evaluated in the CHB group, compared with healthy controls. Expression in patients with HBsAg (+) was higher than that in patients with HBsAg (−). Notably, serum miR-181b and liver HBV DNA levels were significantly correlated ( P < 0.05). Serum miR-181 levels were higher in patients with serum HBV DNA > 10 IU/ml ( P = 0.017), histologic activity index (HAI) >8 ( P = 0.001) and fibrosis score >4 ( P < 0.0001). Liver HBV DNA levels were higher in patients with abnormal alanine aminotransferase (ALT) values ( P = 0.004), serum HBV DNA levels > 10 IU/ml ( P = 0.034) and fibrosis score >4 ( P = 0.006). Using multivariate logistic regression analysis, serum miR-181b was identified as an independent predictor of disease progression (OR 4.172, 95 % CI 1.838-9.473, P = 0.009 for HAI >8; OR 5.387, 95 % CI 2.067-14.036, P = 0.001 for fibrosis score >4). Conclusions: Serum miR-181b is correlated with liver and serum HBV DNA levels as well as disease progression in CHB. [ABSTRACT FROM AUTHOR]