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

Authors

  • Seyedeh Sara Ghorbanhosseini Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  • Mitra Nourbakhsh Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Address: Hemmat Highway, 1449614535, Tehran, Iran, Tel: +98 21 86703109, Fax: +98 21 88622742, E-mail: nourbakhsh.m@iums.ac.ir
  • Mohammad Zangooei Department of Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
  • Zohreh Abdolvahabi Department of Biochemistry and Genetics, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
  • Zahra Bolandghamtpour Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, IUMS, Tehran, Iran
  • Zahra Hesari Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Laboratory Sciences, Faculty of Paramedicine, Golestan University of Medical Sciences, Gorgan, Iran
  • Zeynab Yousefi Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  • Ghodratollah Panahi Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Reza Meshkani Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.17179/excli2018-1748

Keywords:

breast cancer, NAMPT, apoptosis, miR-494, microRNA

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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Published

2019-09-12

How to Cite

Ghorbanhosseini, S. S., Nourbakhsh, M., Zangooei, M., Abdolvahabi, Z., Bolandghamtpour, Z., Hesari, Z., … 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, 838–851. https://doi.org/10.17179/excli2018-1748

Issue

Vol. 18 (2019)

Section

Original articles

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