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MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity

Ghorbanhosseini, S.S. and Nourbakhsh, M. and Zangooei, M. and Abdolvahabi, Z. and Bolandghamtpour, Z. and Hesari, Z. and Yousefi, Z. and Panahi, G. and Meshkani, R. (2019) MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity. EXCLI Journal, 18. pp. 838-851.

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Breast cancer (BC) is the most prevalent cause of cancer-related death in women worldwide. BC is frequently associated with elevated levels of nicotinamide phosphoribosyltransferase (NAMPT) in blood and tumor tissue. MicroRNA-494 (miR-494) has been described to play key anti-tumor roles in human cancers. The aim of the present study was to investigate the inhibitory effect of miR-494 on NAMPT-mediated viability of BC cells. In this experimental study, MCF-7 and MDA-MB-231 cells were cultured and then transfected with miR-494 mimic, miR-494 inhibitor and their negative controls. The mRNA and protein expression of NAMPT were assessed using real-time PCR and Western blotting, respectively. Subsequently, intracellular NAD levels were determined by a colorimetric method. Finally, cell apoptosis was examined by flow cytometry. Bioinformatics evaluations predicted NAMPT as a miR-494 target gene which was confirmed by luciferase reporter assay. Our results showed an inverse relationship between the expression of miR-494 and NAMPT in both MCF-7 and MDA-MB-231 cell lines. miR-494 significantly down-regulated NAMPT mRNA and protein expression and was also able to reduce the cellular NAD content. Cell viability was decreased following miR-494 up-regulation. In addition, apoptosis was induced in MCF-7 and MDA-MB-231 cells by miR-494 mimic. Our findings indicate that miR-494 acts as a tumor suppressor and has an important effect in suppressing the growth of BC cells through NAMPT. Therefore, miR-494 might be considered as a novel therapeutic target for the management of human breast cancer. © 2019, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: messenger RNA; microRNA; microRNA 494; nicotinamide adenine dinucleotide; nicotinamide phosphoribosyltransferase; unclassified drug, 3' untranslated region; apoptosis; Article; breast cancer; cancer inhibition; cell viability; controlled study; down regulation; enzyme activity; enzyme inhibition; gene expression; gene overexpression; human; human cell; MCF-7 cell line; MDA-MB-231 cell line; protein expression; upregulation
Subjects: بیماریهای زنان WP
QU بیوشیمی
آسیب شناسی QZ
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 18 Dec 2019 11:09
Last Modified: 18 Dec 2019 11:09
URI: http://eprints.goums.ac.ir/id/eprint/10460

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