Open AccessAlcohol‐mediated miR‐34a modulates hepatocyte growth and apoptosis
Author(s) -
Iwagami Yoshifumi,
Zou Jing,
Zhang Hongyu,
Cao Kevin,
Ji Chengcheng,
Kim Miran,
Huang ChiungKuei
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13681
Subject(s) - cell growth , apoptosis , microrna , cancer research , cyclin dependent kinase 6 , cyclin e1 , biology , microbiology and biotechnology , hepatocyte , cyclin d1 , sirtuin 1 , cell cycle , chemistry , downregulation and upregulation , biochemistry , gene , in vitro
Micro RNA s (miRs) have been recently shown to be heavily involved in the development of alcoholic liver disease ( ALD ) and suggested as a potential therapeutic target in ALD . The miR‐34a was consistently reported to be significantly elevated in several ALD rodent models, but it remains unclear how miR‐34a modulates the cellular behaviours of hepatocytes in ALD development and progression. This study aims to characterize alcohol‐induced miR‐34a impact on hepatocytes growth and apoptosis. The mi RNA array was performed to assess changes in mi RNA after chronic alcohol feeding. Liver and blood samples were used to examine ALD progression. The miR‐34a was overexpressed in human hepatocytes to evaluate its impact on cell growth and apoptosis. Real‐time quantitative PCR and Western blot were used to determine the growth and apoptosis molecular signalling pathways associated with miR‐34a. Alcohol feeding significantly promoted fatty liver progression, serum ALT levels, apoptosis and miR‐34a expression in rat liver. Overexpression of miR‐34a in human hepatocytes suppressed cell growth signallings, including c‐Met, cyclin D1 and cyclin‐dependent kinase 6 ( CDK 6). The miR‐34a might also inhibit the expression of sirtuin 1 (Sirt1) and its target, B‐cell lymphoma 2. Interestingly, the expression of miR‐34a reverses the suppressive effects of ethanol on cell growth. But, miR‐34a promotes hepatocyte senescence and apoptosis. Although the miR‐34a‐mediated down‐regulation of cell growth‐associated genes may contribute to cell growth retardation, other miR‐34a targets, such as Sirt1, may reverse this phenotype. Future studies will be needed to clarify the role of miR‐34a in ALD progression.