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

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Seyedeh Sara Ghorbanhosseini
Mitra Nourbakhsh
Mohammad Zangooei
Zohreh Abdolvahabi
Zahra Bolandghamtpour
Zahra Hesari
Zeynab Yousefi
Ghodratollah Panahi
Reza Meshkani

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.

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Ghorbanhosseini, S. S., Nourbakhsh, M., Zangooei, M., Abdolvahabi, Z., Bolandghamtpour, Z., Hesari, Z., Yousefi, Z., Panahi, G., & Meshkani, R. (2019). Original article - MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity. EXCLI Journal, 18, 838-851. https://doi.org/10.17179/excli2018-1748
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