In this issue of JCI, two independent groups describe the effects of germline and liver-specific deletion of Mir122a, the predominant liver miRNA. Their findings reveal a critical role for miR-122 in fat and cholesterol metabolism but suggest that other metabolic actions of the liver are independent of miR-122. Knockout mice also displayed hepatic inflammation, fibrosis, and a high incidence of hepatocellular carcinoma, suggesting that miR-122 has a tumor suppressor role in hepatocytes.
Jessica Wen, Joshua R. Friedman
Overview of the consequences of miR-122 loss on hepatocyte function.
The normal functions of the hepatocyte include carbohydrate and lipid metabolism, bilirubin excretion, and detoxification of endogenous compounds and xenobiotics. In this issue, Tsai et al. and Hsu et al. demonstrate that loss of miR-122 results in increased lipid synthesis and decreased lipid export, but other hepatocyte functions are unaltered. Loss of miR-122 also led to increased inflammation and fibrosis, and eventually the development of HCC, suggesting the miR-122 plays a tumor-suppressive role.