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Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhib...

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Autores principales: Bolandghamat Pour, Zahra, Nourbakhsh, Mitra, Mousavizadeh, Kazem, Madjd, Zahra, Ghorbanhosseini, Seyedeh Sara, Abdolvahabi, Zohreh, Hesari, Zahra, Ezzati Mobasser, Samira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824125/
https://www.ncbi.nlm.nih.gov/pubmed/31675930
http://dx.doi.org/10.1186/s12885-019-6221-0
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author Bolandghamat Pour, Zahra
Nourbakhsh, Mitra
Mousavizadeh, Kazem
Madjd, Zahra
Ghorbanhosseini, Seyedeh Sara
Abdolvahabi, Zohreh
Hesari, Zahra
Ezzati Mobasser, Samira
author_facet Bolandghamat Pour, Zahra
Nourbakhsh, Mitra
Mousavizadeh, Kazem
Madjd, Zahra
Ghorbanhosseini, Seyedeh Sara
Abdolvahabi, Zohreh
Hesari, Zahra
Ezzati Mobasser, Samira
author_sort Bolandghamat Pour, Zahra
collection PubMed
description BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhibition by miR-154 was investigated on breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cancer cell lines were transfected with the mimic and inhibitors of miR-154-5p and their corresponding negative controls. Consequently, levels of NAMPT and NAD were assayed employing qRT-PCR, Western blotting and enzymatic method, respectively. Subsequently, flow cytometry and colorimetric methods were performed to evaluate apoptosis and cell viability. Bioinformatics analyses as well as luciferase assay were done to investigate whether the 3′-UTR of NAMPT is directly targeted by miR-154. RESULTS: According to the obtained results, NAMPT was recognized as a target for binding of miR-154 and the levels of this miRNA was inversely associated with both mRNA and protein levels of NAMPT in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell viability and increased rate of cell death. When breast cancer cells were simultaneously treated with doxorubicin and miR-154 mimic, cell viability was considerably reduced compared to treatment with doxorubicin alone in both cell lines. CONCLUSIONS: It was concluded that the inhibition of NAD production by miR-154 might be introduced as an appropriate therapeutic approach in order to improve breast cancer outcome either alone or in combination with other conventional chemotherapeutic agents.
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spelling pubmed-68241252019-11-06 Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin Bolandghamat Pour, Zahra Nourbakhsh, Mitra Mousavizadeh, Kazem Madjd, Zahra Ghorbanhosseini, Seyedeh Sara Abdolvahabi, Zohreh Hesari, Zahra Ezzati Mobasser, Samira BMC Cancer Research Article BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhibition by miR-154 was investigated on breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cancer cell lines were transfected with the mimic and inhibitors of miR-154-5p and their corresponding negative controls. Consequently, levels of NAMPT and NAD were assayed employing qRT-PCR, Western blotting and enzymatic method, respectively. Subsequently, flow cytometry and colorimetric methods were performed to evaluate apoptosis and cell viability. Bioinformatics analyses as well as luciferase assay were done to investigate whether the 3′-UTR of NAMPT is directly targeted by miR-154. RESULTS: According to the obtained results, NAMPT was recognized as a target for binding of miR-154 and the levels of this miRNA was inversely associated with both mRNA and protein levels of NAMPT in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell viability and increased rate of cell death. When breast cancer cells were simultaneously treated with doxorubicin and miR-154 mimic, cell viability was considerably reduced compared to treatment with doxorubicin alone in both cell lines. CONCLUSIONS: It was concluded that the inhibition of NAD production by miR-154 might be introduced as an appropriate therapeutic approach in order to improve breast cancer outcome either alone or in combination with other conventional chemotherapeutic agents. BioMed Central 2019-11-01 /pmc/articles/PMC6824125/ /pubmed/31675930 http://dx.doi.org/10.1186/s12885-019-6221-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bolandghamat Pour, Zahra
Nourbakhsh, Mitra
Mousavizadeh, Kazem
Madjd, Zahra
Ghorbanhosseini, Seyedeh Sara
Abdolvahabi, Zohreh
Hesari, Zahra
Ezzati Mobasser, Samira
Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
title Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
title_full Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
title_fullStr Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
title_full_unstemmed Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
title_short Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
title_sort suppression of nicotinamide phosphoribosyltransferase expression by mir-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824125/
https://www.ncbi.nlm.nih.gov/pubmed/31675930
http://dx.doi.org/10.1186/s12885-019-6221-0
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