Xiang Lan1, Guangyao Li1, Hongming Liu1, Hangwei Fu1, Ping Chen1, Menggang Liu2. 1. Department of Hepatobiliary Surgery, Daping Hospital, The Third Military Medical University (Army Medical University), 10# Changjiangzhilu Daping, Chongqing, 400042, China. 2. Department of Hepatobiliary Surgery, Daping Hospital, The Third Military Medical University (Army Medical University), 10# Changjiangzhilu Daping, Chongqing, 400042, China. Menggang_liu@hotmail.com.
Abstract
BACKGROUND: Transmembrane and ubiquitin-like domain-containing 1 protein (Tmub1) negatively regulates liver regeneration. However, whether this regulation involves posttranscriptional modification of Tmub1 expression is unknown. AIM: The aim of the study was to investigate whether microRNA (miR)-27a/b regulates posttranscriptional modification of Tmub1 and cell proliferation during liver regeneration. METHODS: Tmub1 mRNA 3'-untranslated region (UTR) sequences were analyzed using online software. A luciferase assay was used to verify the relationship between miR-27a/b and the 3'-UTR of Tmub1. Rat partial hepatectomy models were used to investigate miR-27a/b and Tmub1 levels after partial hepatectomy. MiR-27a/b expression was down- and up-regulated with mimics and inhibitors, respectively, to observe the effects of miR-27a/b on Tmub1 expression. Quantitative RT-PCR and Western blot analyses were used to measure miR-27a/b and Tmub1 expression. Hepatocyte proliferation was measured using the CCK8 method for BRL-3A liver cells and proliferating cell nuclear antigen and histone H3 phosphorylation in the regenerating liver. RESULTS: A potential binding site of miR-27a/b was found in the 3'-UTR sequence of Tmub1. Our luciferase assay confirmed that the Tmub1 mRNA 3'-UTR was the target of miR-27a/b. We observed a temporal correlation between miR-27a/b and Tmub1 expression during liver regeneration. MiR-27a/b down-regulated Tmub1 expression both in vivo and in vitro. MiR-27a/b regulated hepatocyte proliferation during liver regeneration. CONCLUSION: MiR-27a/b regulates hepatocyte proliferation by controlling posttranscriptional modification of Tmub1 during liver regeneration.
BACKGROUND:Transmembrane and ubiquitin-like domain-containing 1 protein (Tmub1) negatively regulates liver regeneration. However, whether this regulation involves posttranscriptional modification of Tmub1 expression is unknown. AIM: The aim of the study was to investigate whether microRNA (miR)-27a/b regulates posttranscriptional modification of Tmub1 and cell proliferation during liver regeneration. METHODS:Tmub1 mRNA 3'-untranslated region (UTR) sequences were analyzed using online software. A luciferase assay was used to verify the relationship between miR-27a/b and the 3'-UTR of Tmub1. Rat partial hepatectomy models were used to investigate miR-27a/b and Tmub1 levels after partial hepatectomy. MiR-27a/b expression was down- and up-regulated with mimics and inhibitors, respectively, to observe the effects of miR-27a/b on Tmub1 expression. Quantitative RT-PCR and Western blot analyses were used to measure miR-27a/b and Tmub1 expression. Hepatocyte proliferation was measured using the CCK8 method for BRL-3A liver cells and proliferating cell nuclear antigen and histone H3 phosphorylation in the regenerating liver. RESULTS: A potential binding site of miR-27a/b was found in the 3'-UTR sequence of Tmub1. Our luciferase assay confirmed that the Tmub1 mRNA 3'-UTR was the target of miR-27a/b. We observed a temporal correlation between miR-27a/b and Tmub1 expression during liver regeneration. MiR-27a/b down-regulated Tmub1 expression both in vivo and in vitro. MiR-27a/b regulated hepatocyte proliferation during liver regeneration. CONCLUSION:MiR-27a/b regulates hepatocyte proliferation by controlling posttranscriptional modification of Tmub1 during liver regeneration.
Authors: Rui E Castro; Duarte M S Ferreira; Xiaoxiao Zhang; Pedro M Borralho; Aaron L Sarver; Yan Zeng; Clifford J Steer; Betsy T Kren; Cecília M P Rodrigues Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-08-05 Impact factor: 4.052
Authors: Amy H Buck; Jonathan Perot; Michael A Chisholm; Diwakar S Kumar; Lee Tuddenham; Valérie Cognat; Lisa Marcinowski; Lars Dölken; Sébastien Pfeffer Journal: RNA Date: 2010-01-04 Impact factor: 4.942
Authors: Yana V Kiseleva; Sevak Z Antonyan; Tatyana S Zharikova; Kirill A Tupikin; Dmitry V Kalinin; Yuri O Zharikov Journal: World J Hepatol Date: 2021-03-27