BACKGROUND & AIMS: Epithelial-mesenchymal transition (EMT) has been implicated in the processes of embryogenesis, tissue fibrosis and carcinogenesis. Transforming growth factor-β (TGF-β) has been identified as a key driver of EMT and plays a key role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC). The aim was to identify microRNA (miR) expression in TGF-β-induced hepatocyte EMT. METHODS: We treated a human hepatocyte cell line PH5CH8 with TGF-β to induce an EMT-like change in phenotype and then identified dysregulated miRs using TaqMan Low Density Arrays. MiR expression was altered using miR-181a mimic and inhibitor in the same system and gene changes were identified using TaqMan gene arrays. MiR-181a gene expression was measured in human and mouse cirrhotic or HCC liver tissue samples. Gene changes were identified in rAAV-miR-181a-expressing mouse livers using TaqMan gene arrays. RESULTS: We identified miR-181a as a miR that was significantly up-regulated in response to TGF-β treatment. Over-expression of a miR-181a mimic induced an in vitro EMT-like change with a phenotype similar to that seen with TGF-β treatment alone and was reversed using a miR-181a inhibitor. MiR-181a was shown to be up-regulated in experimental and human cirrhotic and HCC tissue. Mouse livers expressing rAAV-miR-181a showed genetic changes associated with TGF-β signalling and EMT. CONCLUSIONS: MiR-181a had a direct effect in inducing hepatocyte EMT and was able to replace TGF-β-induced effects in vitro. MiR-181a was over-expressed in cirrhosis and HCC and is likely to play a role in disease pathogenesis.
BACKGROUND & AIMS: Epithelial-mesenchymal transition (EMT) has been implicated in the processes of embryogenesis, tissue fibrosis and carcinogenesis. Transforming growth factor-β (TGF-β) has been identified as a key driver of EMT and plays a key role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC). The aim was to identify microRNA (miR) expression in TGF-β-induced hepatocyte EMT. METHODS: We treated a human hepatocyte cell line PH5CH8 with TGF-β to induce an EMT-like change in phenotype and then identified dysregulated miRs using TaqMan Low Density Arrays. MiR expression was altered using miR-181a mimic and inhibitor in the same system and gene changes were identified using TaqMan gene arrays. MiR-181a gene expression was measured in human and mouse cirrhotic or HCC liver tissue samples. Gene changes were identified in rAAV-miR-181a-expressing mouse livers using TaqMan gene arrays. RESULTS: We identified miR-181a as a miR that was significantly up-regulated in response to TGF-β treatment. Over-expression of a miR-181a mimic induced an in vitro EMT-like change with a phenotype similar to that seen with TGF-β treatment alone and was reversed using a miR-181a inhibitor. MiR-181a was shown to be up-regulated in experimental and human cirrhotic and HCC tissue. Mouse livers expressing rAAV-miR-181a showed genetic changes associated with TGF-β signalling and EMT. CONCLUSIONS:MiR-181a had a direct effect in inducing hepatocyte EMT and was able to replace TGF-β-induced effects in vitro. MiR-181a was over-expressed in cirrhosis and HCC and is likely to play a role in disease pathogenesis.
Authors: Vida Chitsazzadeh; Tran N Nguyen; Alvaro de Mingo Pulido; Bruna B Bittencourt; Lili Du; Charles H Adelmann; Ivannie Ortiz Rivera; Kimberly A Nguyen; Leah D Guerra; Andrew Davis; Marco Napoli; Wencai Ma; Richard Eric Davis; Kimal Rajapakshe; Cristian Coarfa; Elsa R Flores; Kenneth Y Tsai Journal: J Invest Dermatol Date: 2021-12-08 Impact factor: 7.590
Authors: Scott M Riester; Diren Arsoy; Emily T Camilleri; Amel Dudakovic; Christopher R Paradise; Jared M Evans; Jorge Torres-Mora; Marco Rizzo; Peter Kloen; Marianna Kruithof-de Julio; Andre J van Wijnen; Sanjeev Kakar Journal: BMC Med Genomics Date: 2015-10-07 Impact factor: 3.063