کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5660303 1590324 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
miR-1224 inhibits cell proliferation in acute liver failure by targeting the antiapoptotic gene Nfib
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
miR-1224 inhibits cell proliferation in acute liver failure by targeting the antiapoptotic gene Nfib
چکیده انگلیسی


- miR-1224 is up-regulated in the livers and serum of mice after induction of liver injury.
- miR-1224 is up-regulated in the livers and serum of patients with ALF and indicates a poor prognosis.
- Upregulated miR-1224 represses proliferation and induces apoptosis in hepatocytes during ALF by targeting Nfib.

Background and AimsPatient outcome in acute liver failure (ALF) is crucially determined by the appropriate balance between cell death and compensatory cell proliferation. MicroRNAs (miRNAs) - small non-coding RNAs that function as guide molecules in RNA silencing - have evolved as crucial mediators of nearly all developmental and pathological processes, including the physiology and pathology of the liver. We investigated the role of miR-1224 during ALF.MethodsWe measured miR-1224 in livers of mice in various acute liver disease murine models and in, patients with ALF, using quantitative real-time PCR. We studied the regulation of miR-1224 in AML12 cells and primary hepatocytes upon H2O2 stimulation. Cell proliferation and cell death were analysed by 5-bromo-2′-deoxyuridine and terminal deoxynucleotide transferase nick end labelling stainings, respectively.ResultsWe found that miR-1224 was up-regulated in hepatocytes upon ischaemia-reperfusion in vivo and in vitro. This was accompanied by impaired proliferation and elevated apoptosis. This function of miR-1224 was mediated by repressing the anti-apoptotic gene Nfib in hepatocytes. Strikingly, miR-1224 was also up-regulated in human livers and the serum of patients with ALF and indicated an unfavourable prognosis with an excellent prognostic value compared to other known serum markers in this clinical setting.ConclusionsmiR-1224 is a previously unrecognised regulator of proliferation after ALF in hepatocytes and represents a novel and specific biomarker of liver injury with prognostic value in ALF. Thus, miR-1224 may represent a target for novel therapeutic and diagnostic strategies in the context of ALF and warrants further testing as a biomarker in prospective trials.Lay summary: In acute liver failure, miR-1224 expression is modulated by oxidative stress. This leads to a decrease in hepatocyte cell proliferation and increase in apoptosis. Increased serum levels of miR-1224 could be a useful diagnostic marker in patients with acute liver failure.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 67, Issue 5, November 2017, Pages 966-978
نویسندگان
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