4.6 Article Retracted Publication

被撤回的出版物: MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1 (Retracted article. See vol. 63, 2023)

Journal

INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 45, Issue 5, Pages 2143-2152

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2014.2596

Keywords

microRNA; SIRT1; proliferation; SREBP-1c; lipid metabolism; hepatocellular carcinoma

Categories

Funding

  1. National Natural Science Foundation of China [30600524, 81341067, 81071990, 81201758]
  2. Science and Technology Planning Project of Guangdong Province [2012A030400055, 2010B080701088, 2011B080701096, 2011B031800184]
  3. Science and Technology projects of Guangzhou [20111410010, 2011J4300066]
  4. Special Project of Beijing Health Development and Scientific Research, China [2011-5041-02]
  5. 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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