Golestan University of Medical Sciences Repository

Up-regulation of MIR-381 inhibits NAD+ salvage pathway and promotes apoptosis in breast cancer cells

Pour, Z.B. and Nourbakhsh, M. and Mousavizadeh, K. and Madjd, Z. and Ghorbanhosseini, S.S. and Abdolvahabi, Z. and Hesari, Z. and Mobaser, S.E. (2019) Up-regulation of MIR-381 inhibits NAD+ salvage pathway and promotes apoptosis in breast cancer cells. EXCLI Journal, 18. pp. 683-696.

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Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme involved in nicotinamide adenine dinucleotide (NAD) salvage pathway, is overexpressed in many human malignancies such as breast cancer. This enzyme plays a critical role in survival and growth of cancer cells. MicroRNAs (miRNAs) are among the most important regulators of gene expression, and serve as potential targets for diagnosis, prognosis, and therapy of breast cancer. Therefore, the aim of this study was to assess the effect of NAMPT inhibition by miR-381 on breast cancer cell survival. MCF-7 and MDA-MB-231 cancer cell lines were transfected with miR-381 mimic, inhibitor, and their corresponding negative controls (NCs). Subsequently, the level of NAMPT and NAD was assessed using real-time PCR, immuno-blotting, and enzymatic methods, respectively. In order to evaluate apoptosis, cells were labelled with Annexin V-FITC and propidium iodide and analyzed by flow cytometry. Bioinformatics analysis was performed to recognize whether NAMPT 3�-untranslated region (UTR) is a direct target of miR-381 and the results were authenticated by the luciferase reporter assay using a vector containing the 3�-UTR sequence of NAMPT. Our results revealed that the 3�-UTR of NAMPT was a direct target of miR-381 and its up-regulation decreased NAMPT gene and protein expression, leading to a notable reduction in intracellular NAD and subsequently cell survival and induction of apoptosis. It can be concluded that miR-381 has a vital role in tumor suppression by down-regulation of NAMPT, and it can be a promising candidate for breast cancer therapy. © 2019, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: fluorescein isothiocyanate; lipocortin 5; microRNA; microRNA 381; nicotinamide adenine dinucleotide; nicotinamide phosphoribosyltransferase; propidium iodide; unclassified drug, 3' untranslated region; apoptosis; Article; bioinformatics; breast cancer; cancer inhibition; cell survival; controlled study; enzyme analysis; enzyme inhibition; flow cytometry; genetic transfection; HEK293T cell line; human; human cell; immunoblotting; luciferase assay; MCF-10A cell line; MCF-7 cell line; MDA-MB-231 cell line; protein expression; protein targeting; real time polymerase chain reaction; upregulation
Subjects: بیماریهای زنان WP
آسیب شناسی QZ
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 16 Dec 2019 11:42
Last Modified: 16 Dec 2019 11:42
URI: http://eprints.goums.ac.ir/id/eprint/10428

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