MicroRNA-148a deficiency promotes hepatic lipid metabolism and hepatocarcinogenesis in mice.

Abstract:

:miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here miR-148a knockout (KO) mice were used to investigate the intrinsic role of miR-148a in liver physiology and hepatocarcinogenesis in mice. miR-148a downregulation was found to be correlated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients. Under regular chow diet (RCD) or high fat diet (HFD), miR-148a deletion significantly accelerated DEN-induced hepatocarcinogenesis in mice. Mechanistically, miR-148a deletion promotes lipid metabolic disorders in mice. Moreover, restoration of miR-148a reversed these defects. Finally, miR-148a was found to directly inhibit several key regulators of hepatocarcinogenesis and lipid metabolism. These findings reveal crucial roles for miR-148a in the hepatic lipid metabolism and hepatocarcinogenesis. They further identify miR-148a as a potential therapeutic target for certain liver diseases, including cancer.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Cheng L,Zhu Y,Han H,Zhang Q,Cui K,Shen H,Zhang J,Yan J,Prochownik E,Li Y

doi

10.1038/cddis.2017.309

subject

Has Abstract

pub_date

2017-07-13 00:00:00

pages

e2916

issue

7

issn

2041-4889

pii

cddis2017309

journal_volume

8

pub_type

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