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Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

Sialylation is one of the altered glycosylation patterns associated with cancer progression. In this study, we investigated the N-glycan profiles of breast cancer patients and cell lines to reveal sialylation associated with breast cancer progression, and provided new evidences of miRNA-mediated sia...

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Detalles Bibliográficos
Autores principales: Ma, Xiaolu, Dong, Weijie, Su, Zhen, Zhao, Lifen, Miao, Yuan, Li, Nana, Zhou, Huimin, Jia, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260976/
https://www.ncbi.nlm.nih.gov/pubmed/28032858
http://dx.doi.org/10.1038/cddis.2016.427
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author Ma, Xiaolu
Dong, Weijie
Su, Zhen
Zhao, Lifen
Miao, Yuan
Li, Nana
Zhou, Huimin
Jia, Li
author_facet Ma, Xiaolu
Dong, Weijie
Su, Zhen
Zhao, Lifen
Miao, Yuan
Li, Nana
Zhou, Huimin
Jia, Li
author_sort Ma, Xiaolu
collection PubMed
description Sialylation is one of the altered glycosylation patterns associated with cancer progression. In this study, we investigated the N-glycan profiles of breast cancer patients and cell lines to reveal sialylation associated with breast cancer progression, and provided new evidences of miRNA-mediated sialylation. MALDI-TOF MS analysis revealed that N-glycans found in breast cancer tissues and breast cancer cell MDA-MB-231 featured increased levels of sialylation compared with adjacent tissues and normal breast epithelial cell MCF-10A. The expressional profiles of 20 sialyltransferase genes were then analyzed and found significantly different comparing breast cancer samples with adjacent tissues, and two breast cancer cell lines MDA-MB-231 and MCF-7 with different metastatic potential and MCF-10A cells. Tumor tissues and highly metastatic breast cancer cell line MDA-MB-231 exhibited higher levels of ST8SIA4. Knocking down ST8SIA4 in breast cancer cell lines significantly inhibited their malignant behaviors including cell proliferation and invasion in a sialyltransferase-dependent manner. By applying bioinformatic approaches for the prediction of miRNA targeting 3′-UTR of ST8SIA4, we identified ST8SIA4 as one of the miR-26a/26b-targeted genes. Further data analysis revealed the inversely related expression of ST8SIA4 and miR-26a/26b in breast cancer cells, tumor tissues and corresponding adjacent tissues. The ability of miR-26a/26b to interact specifically with and regulate the 3′-UTR of ST8SIA4 was demonstrated via a luciferase reporter assay. The forced expression of miR-26a/26b was able to induce a decrease of ST8SIA4 level and also to affect breast cancer cells progression, while altered expression of ST8SIA4 in breast cancer cells modulated progression upon transfection with miR-26a/26b mimics or inhibiter. Taken together, these results indicate that changes in the glycosylation patterns and sialylation levels may be useful markers of the progression of breast cancer, as well as miR-26a/26b may be widely involved in the regulation of sialylation machinery by targeting ST8SIA4.
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spelling pubmed-52609762017-01-26 Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4 Ma, Xiaolu Dong, Weijie Su, Zhen Zhao, Lifen Miao, Yuan Li, Nana Zhou, Huimin Jia, Li Cell Death Dis Original Article Sialylation is one of the altered glycosylation patterns associated with cancer progression. In this study, we investigated the N-glycan profiles of breast cancer patients and cell lines to reveal sialylation associated with breast cancer progression, and provided new evidences of miRNA-mediated sialylation. MALDI-TOF MS analysis revealed that N-glycans found in breast cancer tissues and breast cancer cell MDA-MB-231 featured increased levels of sialylation compared with adjacent tissues and normal breast epithelial cell MCF-10A. The expressional profiles of 20 sialyltransferase genes were then analyzed and found significantly different comparing breast cancer samples with adjacent tissues, and two breast cancer cell lines MDA-MB-231 and MCF-7 with different metastatic potential and MCF-10A cells. Tumor tissues and highly metastatic breast cancer cell line MDA-MB-231 exhibited higher levels of ST8SIA4. Knocking down ST8SIA4 in breast cancer cell lines significantly inhibited their malignant behaviors including cell proliferation and invasion in a sialyltransferase-dependent manner. By applying bioinformatic approaches for the prediction of miRNA targeting 3′-UTR of ST8SIA4, we identified ST8SIA4 as one of the miR-26a/26b-targeted genes. Further data analysis revealed the inversely related expression of ST8SIA4 and miR-26a/26b in breast cancer cells, tumor tissues and corresponding adjacent tissues. The ability of miR-26a/26b to interact specifically with and regulate the 3′-UTR of ST8SIA4 was demonstrated via a luciferase reporter assay. The forced expression of miR-26a/26b was able to induce a decrease of ST8SIA4 level and also to affect breast cancer cells progression, while altered expression of ST8SIA4 in breast cancer cells modulated progression upon transfection with miR-26a/26b mimics or inhibiter. Taken together, these results indicate that changes in the glycosylation patterns and sialylation levels may be useful markers of the progression of breast cancer, as well as miR-26a/26b may be widely involved in the regulation of sialylation machinery by targeting ST8SIA4. Nature Publishing Group 2016-12 2016-12-29 /pmc/articles/PMC5260976/ /pubmed/28032858 http://dx.doi.org/10.1038/cddis.2016.427 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Ma, Xiaolu
Dong, Weijie
Su, Zhen
Zhao, Lifen
Miao, Yuan
Li, Nana
Zhou, Huimin
Jia, Li
Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4
title Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4
title_full Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4
title_fullStr Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4
title_full_unstemmed Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4
title_short Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4
title_sort functional roles of sialylation in breast cancer progression through mir-26a/26b targeting st8sia4
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260976/
https://www.ncbi.nlm.nih.gov/pubmed/28032858
http://dx.doi.org/10.1038/cddis.2016.427
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