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Microrna-494 Induces Breast Cancer Cell Apoptosis and Reduces Cell Viability by Inhibition of Nicotinamide Phosphoribosyltransferase Expression and Activity Publisher



Ghorbanhosseini SS1 ; Nourbakhsh M1 ; Zangooei M2 ; Abdolvahabi Z3 ; Bolandghamtpour Z4 ; Hesari Z5, 6 ; Yousefi Z1 ; Panahi G7 ; Meshkani R7
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Authors Affiliations
  1. 1. Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
  3. 3. Department of Biochemistry and Genetics, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
  4. 4. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, IUMS, Tehran, Iran
  5. 5. Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
  6. 6. Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, Gorgan, Iran
  7. 7. Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: EXCLI Journal Published:2019


Abstract

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.
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