Iron depletion participates in the suppression of cell proliferation induced by lipin1 overexpression
Abstract
Lipin1 participates in numerous cellular processes, including in the dephosphorylation of phosphatidic acid to diacylglycerol and as a co-transcriptional regulator. Iron is also essential in various critical biological processes. Previous studies have shown that compared to normal tissue cells, lipin1 expression and iron metabolism are abnormal in cancer cells. However, the involvement of lipin1 in the regulation of iron metabolism is unknown. In this study, we compared the contents of eight metal ions (potassium, calcium, sodium, magnesium, manganese, zinc, iron and copper) in human hepatoma carcinoma BEL7402 control cells as well as stable cells overexpressing lipin1 by using ICP-AES. Our results showed that only intracellular iron content was significantly decreased by lipin1 overexpression. Meanwhile, we observed that lipin1 overexpression could inhibit cell proliferation, similar to iron chelator deferoxamine. Western blotting showed that the up-regulation of p53-p21-p27 elicited cell cycle G0/G1 arrest in the stable cells overexpressing lipin1. Conversely, after lipin1 was down regulated with siRNA, we found that cell proliferation was promoted, accompanied by an increase in iron content, and the downregulation of p53 and...Continue Reading
References
Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing
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