The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Disruption of Dicer1 Induces Dysregulated Fetal Gene Expression and Promotes Hepatocarcinogenesis
Open accessAbstract
Background and Aims Growing evidence suggests that microRNAs coordinate various biological processes in the liver. We describe experiments to address the physiological roles of these new regulators of gene expression in the liver that are as of yet largely undefined. Methods We disrupted Dicer, an enzyme essential for the processing of microRNAs, in hepatocytes using a conditional knockout mouse model to elucidate the consequences of loss of microRNAs. Results The conditional knockout mouse livers showed the efficient disruption of Dicer1 at 3 weeks after birth. This resulted in prominent steatosis and the depletion of glycogen storage. Dicer1-deficient liver exhibited increased growth-promoting gene expression and the robust expression of fetal stage-specific genes. The consequence of Dicer elimination included both increased hepatocyte proliferation as well as overwhelming apoptosis. Over time, Dicer1-expressing wild-type hepatocytes that had escaped Cre-mediated recombination progressively repopulated the entire liver. Unexpectedly, however, two-third of the mutant mice spontaneously developed hepatocellular carcinomas derived from residual Dicer1-deficient hepatocytes at 1 year old. Conclusions Dicer and microRNAs have critical roles in hepatocyte survival, metabolism, developmental gene regulation and tumor suppression in the liver. Loss of Dicer primarily impairs hepatocyte survival, but can promote hepatocarcinogenesis in cooperation with additional oncogenic stimuli.
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MicroRNAs in Development and Disease
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Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease
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Recurrent Somatic DICER1 Mutations in Nonepithelial Ovarian Cancers
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Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis
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Metadata
- Authors
- Sekine, S., Ogawa, R., Ito, R., Hiraoka, N., McManus, M. T., Kanai, Y., & Hebrok, M.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 136
- Issue
- 7
- Pages
- 2304-2315.e4
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2082381304
- Cited by
- 181
- References
- 7
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sekine, S., Ogawa, R., Ito, R., Hiraoka, N., McManus, M. T., Kanai, Y., & Hebrok, M. (2009). Disruption of Dicer1 Induces Dysregulated Fetal Gene Expression and Promotes Hepatocarcinogenesis. Gastroenterology. https://doi.org/10.1053/j.gastro.2009.02.067
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