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miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression

Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expressi...

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Autores principales: Hou, Xiaoke, Niu, Zhaofeng, Liu, Leilei, Guo, Qiang, Li, Haiyang, Yang, Xiaojun, Zhang, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312986/
https://www.ncbi.nlm.nih.gov/pubmed/30655858
http://dx.doi.org/10.3892/ol.2018.9687
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author Hou, Xiaoke
Niu, Zhaofeng
Liu, Leilei
Guo, Qiang
Li, Haiyang
Yang, Xiaojun
Zhang, Xia
author_facet Hou, Xiaoke
Niu, Zhaofeng
Liu, Leilei
Guo, Qiang
Li, Haiyang
Yang, Xiaojun
Zhang, Xia
author_sort Hou, Xiaoke
collection PubMed
description Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expression levels of microRNA (miR)-1207-5p in human normal breast epithelial MCF-10A cells and TNBC cell lines (MDA-MB-231, MDA-MB-436 and MDA-MB-453). The results revealed that the highest miR-1207-5p level was in MDA-MB-231, which suggested an oncogenic role of miR-1207-5p in TNBC. Therefore, MDA-MB-231 served as the present study's research model in subsequent experiments. The mRNAs that functioned as tumor suppressor factors for miR-1207-5p were then determined. Leucine zipper tumor suppressor gene 1 (LZTS1), which was predicted by TargetScan 6.2 and was supported by the results of a dual luciferase assay, was identified as a target of miR-1207-5p. AntagomiR-1207-5p increased LZTS1 mRNA and protein expressions, enhanced cell growth arrest and cell apoptosis induced by Taxol in MDA-MB-231 cells. Additionally, it was observed that, when compared with Taxol treatment, the combination of Taxol and antagomiR-1207-5p induced a sharp decrease in B-cell lymphoma 2 (Bcl-2) and phosphorylated-protein kinase B expression accompanied by an increase in the Bcl-2-associated X protein expression. Finally, miR-1207-5p expression was significantly increased, while LZTS1 expression was significantly decreased, in TNBC tissues when compared with normal adjacent tissues, and there was a negative correlation between miR-1207-5p and LZTS1 expression. In addition, there was a notable elevation in the expression of miR-1207-5p and a reduction in the expression of LZTS1 in the Taxol non-responsive TNBC tissues when compared with the Taxol-responsive TNBC tissues. The results of the present study suggested that miR-1207-5p may be a promising predictor of sensitivity towards Taxol in TNBC.
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spelling pubmed-63129862019-01-17 miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression Hou, Xiaoke Niu, Zhaofeng Liu, Leilei Guo, Qiang Li, Haiyang Yang, Xiaojun Zhang, Xia Oncol Lett Articles Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expression levels of microRNA (miR)-1207-5p in human normal breast epithelial MCF-10A cells and TNBC cell lines (MDA-MB-231, MDA-MB-436 and MDA-MB-453). The results revealed that the highest miR-1207-5p level was in MDA-MB-231, which suggested an oncogenic role of miR-1207-5p in TNBC. Therefore, MDA-MB-231 served as the present study's research model in subsequent experiments. The mRNAs that functioned as tumor suppressor factors for miR-1207-5p were then determined. Leucine zipper tumor suppressor gene 1 (LZTS1), which was predicted by TargetScan 6.2 and was supported by the results of a dual luciferase assay, was identified as a target of miR-1207-5p. AntagomiR-1207-5p increased LZTS1 mRNA and protein expressions, enhanced cell growth arrest and cell apoptosis induced by Taxol in MDA-MB-231 cells. Additionally, it was observed that, when compared with Taxol treatment, the combination of Taxol and antagomiR-1207-5p induced a sharp decrease in B-cell lymphoma 2 (Bcl-2) and phosphorylated-protein kinase B expression accompanied by an increase in the Bcl-2-associated X protein expression. Finally, miR-1207-5p expression was significantly increased, while LZTS1 expression was significantly decreased, in TNBC tissues when compared with normal adjacent tissues, and there was a negative correlation between miR-1207-5p and LZTS1 expression. In addition, there was a notable elevation in the expression of miR-1207-5p and a reduction in the expression of LZTS1 in the Taxol non-responsive TNBC tissues when compared with the Taxol-responsive TNBC tissues. The results of the present study suggested that miR-1207-5p may be a promising predictor of sensitivity towards Taxol in TNBC. D.A. Spandidos 2019-01 2018-11-12 /pmc/articles/PMC6312986/ /pubmed/30655858 http://dx.doi.org/10.3892/ol.2018.9687 Text en Copyright: © Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Hou, Xiaoke
Niu, Zhaofeng
Liu, Leilei
Guo, Qiang
Li, Haiyang
Yang, Xiaojun
Zhang, Xia
miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression
title miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression
title_full miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression
title_fullStr miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression
title_full_unstemmed miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression
title_short miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression
title_sort mir-1207-5p regulates the sensitivity of triple-negative breast cancer cells to taxol treatment via the suppression of lzts1 expression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312986/
https://www.ncbi.nlm.nih.gov/pubmed/30655858
http://dx.doi.org/10.3892/ol.2018.9687
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