MicroRNA-494 induces breast cancer cell apoptosis and reduces cell viability by inhibition of nicotinamide phosphoribosyltransferase expression and activity
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Date
2019-09-12
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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.
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Keywords
Breast cancer, NAMPT, Apoptosis, miR-494, microRNA