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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

Bolandghamat Pour, Z. and Nourbakhsh, M. and Mousavizadeh, K. and Madjd, Z. and Ghorbanhosseini, S.S. and Abdolvahabi, Z. and Hesari, Z. and Ezzati Mobasser, S. (2019) Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin. BMC Cancer, 19 (1).

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Abstract

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. © 2019 The Author(s).

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: doxorubicin; microRNA; microRNA 154; nicotinamide adenine dinucleotide; nicotinamide phosphoribosyltransferase; unclassified drug, 3' untranslated region; apoptosis; Article; bioinformatics; breast cancer cell line; cell death; cell viability; controlled study; drug mechanism; drug sensitivity; enzyme inhibition; flow cytometry; gene expression; gene targeting; luciferase assay; MCF-7 cell line; MDA-MB-231 cell line; protein expression; quantitative analysis; real time polymerase chain reaction; RNA binding; Western blotting
Subjects: بیماریهای زنان WP
آسیب شناسی QZ
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 10 Dec 2019 08:18
Last Modified: 10 Dec 2019 08:18
URI: http://eprints.goums.ac.ir/id/eprint/10360

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