Authors: | Ghorbanhosseini, Seyedeh Sara Nourbakhsh, Mitra Zangooei, Mohammad Abdolvahabi, Zohreh Bolandghamtpour, Zahra Hesari, Zahra Yousefi, Zeynab Panahi, Ghodratollah Meshkani, Reza |
Title: | MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity |
Language (ISO): | en |
Abstract: | Breast cancer (BC) is the most preval ent cause of cancer-related death in women worldwide. BC is frequently associated with elevated levels of nicotinamide phosphoribos yltransferase (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 transfec ted 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. Subseq uently, intracellular NAD levels were determined by a colorimetric method. Finally, cell apoptosis was examined by fl ow cytometry. Bioinformatics evaluations pre- dicted 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 fo llowing 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. |
Subject Headings: | Breast cancer NAMPT Apoptosis miR-494 microRNA |
URI: | http://hdl.handle.net/2003/39052 http://dx.doi.org/10.17877/DE290R-20971 |
Issue Date: | 2019-09-12 |
Rights link: | http://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Original Articles |
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File | Description | Size | Format | |
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Nourbakhsh_12092019_proof.pdf | DNB | 1.52 MB | Adobe PDF | View/Open |
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