Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 45, Issue 5, Pages 2143-2152Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2014.2596
Keywords
microRNA; SIRT1; proliferation; SREBP-1c; lipid metabolism; hepatocellular carcinoma
Categories
Funding
- National Natural Science Foundation of China [30600524, 81341067, 81071990, 81201758]
- Science and Technology Planning Project of Guangdong Province [2012A030400055, 2010B080701088, 2011B080701096, 2011B031800184]
- Science and Technology projects of Guangzhou [20111410010, 2011J4300066]
- Special Project of Beijing Health Development and Scientific Research, China [2011-5041-02]
- Key Projects in the PLA's logistics Program during the Twelfth Five-year Plan Period [BWS11J029]
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MicroRNA (miRNA or miR) inhibition of oncogenic related pathways has been shown to be a promising therapeutic approach for cancer. SIRT1 might be a promoter factor on tumorigenesis of hepatocellular carcinoma (HCC). However, the mechanism is unknown. We investigated whether miRNAs regulate the SIRT1 and its downstream SREBP-lipogenesis-cholesterogenesis metabolic pathway in hepatoma cells. Human hepatoma cells were transfected with miR-449 mimics and inhibitors, and the effects of miR-449 on cell proliferation was assessed. We identified the miRNAs, miR-449, that control lipogenesis and cholesterogenesis in hepatoma cells by inhibiting SIRT1 and SREBP-1c expression and downregulating their targeted genes, including fatty acid synthase (FASN) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). MiR-449 repressed DNA synthesis, mitotic entry and proliferation of hepatoma cells. Restoration of miR-449 led to suppression of SIRT1 expression and liver tumorigenesis. The newly identified miRNAs, miR-449 represents a novel targeting mechanism for HCC therapy.
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