LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition.

Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.

Impact of sarcopenia on outcomes of patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Previous studies have indicated that sarcopenia is associated with poor post-operative outcomes in liver cancer patients, but the studies are limited by confounding from mixed diseases, retrospective data, and non-standardized measurement methods. At present, there is no research with both muscle mass and strength as predictors for hepatocellular carcinoma (HCC) outcomes. We studied the impact of sarcopenia on post-operative outcomes in HCC patients in a cohort study designed according to the European Working Group on Sarcopenia in Older People standards. METHODS: A total of 781 consecutive patients admitted to our centre were registered from May 2020 to August 2021. All participants submitted questionnaires and underwent handgrip strength, chair stand test, physical performance, and computed tomographic evaluation. Then, they were divided into three groups according to muscle mass and strength: Group A (reduced muscle mass and strength), Group B (reduced muscle strength or reduced muscle mass), and Group C (normal muscle mass and strength). The baseline data and post-operative outcomes were compared and analysed. The primary outcome variable in this study was the presence of a major post-operative complication, and the secondary outcome was the 90-day re-admission rate. RESULTS: A total of 155 patients [median age, 60.00 (IQR, 51.00-66.00) years; 20 females (12.90%)] were included after strict exclusion. The mean (SD) BMI was 23.37 ± 0.23 kg/m2 . The mean (SD) SMI of all participants was 47.05 ± 0.79 cm2 /m2 , and the mean (SD) handgrip strength was 32.84 ± 0.69 kg. Among them, 77 (49.68%) patients underwent laparoscopic hepatectomy, and 73 (47.10%) patients received major hepatectomy. Regarding the post-operative results, Group A had a higher rate of major complications [40.91% (9 of 22) vs. 11.94% (8 of 67) in Group B and 6.06 (4 of 66) in Group C; P = 0.001], higher rate of blood transfusion (77.27% vs. 46.27% in Group B and 42.42% in Group C; P = 0.015), higher hospitalization expenses (P = 0.001), and longer hospital stay (P < 0.001). There was no difference in 90-day re-admission rates among the three groups. Sarcopenia (hazard ratio, 10.735; 95% CI, 2.547-45.244; P = 0.001) and open surgery (hazard ratio, 4.528; 95% CI, 1.425-14.387; P = 0.010) were independent risk factors associated with major complications. CONCLUSIONS: Sarcopenia is associated with adverse outcomes after liver resection for HCC. It should be evaluated upon admission to classify high-risk patients and reduce the risk of major complications.