ArticleThe American journal of pathology2013
Hepatic loss of miR-122 predisposes mice to hepatobiliary cyst and hepatocellular carcinoma upon diethylnitrosamine exposure.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting Chemical-induced Hepatocellular Carcinoma: Ameliorative Potential of Natural Compounds with Focus on Beta-carbolines.Mini reviews in medicinal chemistry · 2026Review
- Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.Cell death and differentiation · 2025Article
- Dysregulation of Lipid and Glucose Homeostasis in Hepatocyte-Specific SLC25A34 Knockout Mice.The American journal of pathology · 2022Article
- Molecular Targets and Signaling Pathways of microRNA-122 in Hepatocellular Carcinoma.Pharmaceutics · 2022Review
- Review
- Histone Methyltransferase G9a-Promoted Progression of Hepatocellular Carcinoma Is Targeted by Liver-Specific Hsa-miR-122.Cancers · 2021Article
- A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma.International journal of molecular sciences · 2020Article
- Akkermansia muciniphila Prevents Fatty Liver Disease, Decreases Serum Triglycerides, and Maintains Gut Homeostasis.Applied and environmental microbiology · 2020Article
- IntestinalBioMed research international · 2020Article
- MicroRNAs and their role in environmental chemical carcinogenesis.Environmental geochemistry and health · 2019Review
- MicroRNA 122, Regulated by GRLH2, Protects Livers of Mice and Patients From Ethanol-Induced Liver Disease.Gastroenterology · 2018Article
- Bioinformatics analysis of gene expression alterations in microRNA‑122 knockout mice with hepatocellular carcinoma.Molecular medicine reports · 2017Article
- MicroRNA-122 regulates polyploidization in the murine liver.Hepatology (Baltimore, Md.) · 2016Article
- Mouse models of liver cancer: Progress and recommendations.Oncotarget · 2015Review
- miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir.Current gene therapy · 2015Review
- Axl as a mediator of cellular growth and survival.Oncotarget · 2014Review
- Article
- MicroRNAs as monitoring markers for right-sided heart failure and congestive hepatopathy.Journal of medicine and lifeReview
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Loss of miR-122 causes chronic steatohepatitis and spontaneous hepatocellular carcinoma. However, the consequence of miR-122 deficiency on genotoxic stress-induced liver pathogenesis is poorly understood. Here, we investigated the impact of miR-122 depletion on liver pathobiology by treating liver-specific miR-122 knockout (LKO) mice with the hepatocarcinogen diethylnitrosamine (DEN). At 25 weeks post-DEN injection, all LKO mice developed CK-19-positive hepatobiliary cysts, which correlated with DEN-induced transcriptional activation of Cdc25a mediated through E2f1. Additionally, LKO livers were more fibrotic and vascular, and developed larger microscopic tumors, possibly due to elevation of the Axl oncogene, a receptor tyrosine kinase as a novel target of miR-122, and several protumorigenic miR-122 targets. At 35 weeks following DEN exposure, LKO mice exhibited a higher incidence of macroscopic liver tumors (71%) and cysts (86%) compared to a 21.4% and 0% incidence of tumors and cysts, respectively, in control mice. The tumors in LKO mice were bigger (ninefold, P = 0.015) and predominantly hepatocellular carcinoma, whereas control mice mostly developed hepatocellular adenoma. DEN treatment also reduced survival of LKO mice compared to control mice (P = 0.03). Interestingly, induction of oxidative stress and proinflammatory cytokines in LKO liver shortly after DEN exposure indicates predisposition of a pro-tumorigenic microenvironment. Collectively, miR-122 depletion facilitates cystogenesis and hepatocarcinogenesis in mice on DEN challenge by up-regulating several genes involved in proliferation, growth factor signaling, neovascularization, and metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.