The Downregulation of CRIF1 Exerts Antitumor Effects Partially via TP53-Induced Glycolysis and Apoptosis Regulator Induction in BT549 Breast Cancer Cells.
Shuyu Piao, Seonhee Kim, Giang-Huong Vu, Minsoo Kim, Eun-Ok Lee, Byeong Hwa Jeon, Cuk-Seong Kim
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引用次数: 0
Abstract
Background/objectives: Mitochondrial oxidative phosphorylation (OXPHOS) has been exploited as a therapeutic target in cancer treatments because of its crucial role in tumorigenesis. CR6-interacting factor 1 (CRIF1), a mitochondrial ribosomal subunit protein, is essential for the regulation of mitochondrial OXPHOS capacity. However, the mechanism of CRIF1 in triple-negative breast cancer (TNBC) cells remains unclear.
Methods/results: We showed that the downregulation of CRIF1 reduced cell proliferation in the TNBC cell lines MDA-MB-468, MDA-MB-231, and, especially, BT549. In addition, wound scratch and Transwell assays showed that CRIF1 deficiency inhibited the migration and invasion of BT549 cells. CRIF1 downregulation resulted in the suppression of mitochondrial bioenergetics in BT549 cells, specifically affecting the inhibition of OXPHOS complexes I and II. This was evidenced by a decrease in the mitochondrial oxygen consumption rate and the depolarization of the mitochondrial membrane potential. Damage to mitochondria resulted in a lower adenosine triphosphate level and an elevated production of mitochondrial reactive oxygen species. In addition, CRIF1 deficiency decreased hypoxia-inducible factor 1α accumulation, NADPH synthesis, and TP53-induced glycolysis and apoptosis regulator (TIGAR) expression in BT549 cells. These events contributed to G0/G1-phase cell cycle inhibition and the upregulation of the cell cycle protein markers p53, p21, and p16. Transfection with a TIGAR overexpression plasmid reversed these effects and prevented CRIF1 downregulation-induced proliferation and migration reduction.
Conclusions: These results indicate that blocking mitochondrial OXPHOS synthesis via CRIF1 may have a therapeutic antitumor effect in BT549 TNBC cells.
期刊介绍:
Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.