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New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis

BACKGROUND: Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. METHODS: Four mRNA datasets and two lncRNA datasets of bone metastasis,...

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Autores principales: Zhang, Yu, Huang, Xiaofeng, Liu, Jin, Chen, Guo, Liu, Chengjun, Zhang, Sen, Li, Jiaxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276423/
https://www.ncbi.nlm.nih.gov/pubmed/34256750
http://dx.doi.org/10.1186/s12935-021-02068-7
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author Zhang, Yu
Huang, Xiaofeng
Liu, Jin
Chen, Guo
Liu, Chengjun
Zhang, Sen
Li, Jiaxin
author_facet Zhang, Yu
Huang, Xiaofeng
Liu, Jin
Chen, Guo
Liu, Chengjun
Zhang, Sen
Li, Jiaxin
author_sort Zhang, Yu
collection PubMed
description BACKGROUND: Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. METHODS: Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. RESULTS: A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. CONCLUSIONS: We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02068-7.
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spelling pubmed-82764232021-07-13 New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis Zhang, Yu Huang, Xiaofeng Liu, Jin Chen, Guo Liu, Chengjun Zhang, Sen Li, Jiaxin Cancer Cell Int Primary Research BACKGROUND: Bone is the most common site of metastatic breast cancer, and it is a leading cause of breast cancer-related death. This study aimed to explore bone metastasis-related long non-coding RNAs (lncRNAs) in breast cancer. METHODS: Four mRNA datasets and two lncRNA datasets of bone metastasis, lung metastasis and liver metastasis of breast cancer were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, as well as the overlap of the two groups, were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) network construction of DEmRNAs were conducted. The cis nearby-targeted DEmRNAs of DElncRNAs were obtained. Quantitative real-time polymerase chain reactions (qRT-PCR) was used to detect the expression levels of selected DEmRNAs and DElncRNAs. LOC641518-lymphoid enhancer-binding factor 1 (LEF1) pair was selected to verify its role in migration and invasion capability of breast cancer cells by wounding healing assay and transwell invasion assay. RESULTS: A total of 237 DEmRNAs were obtained in bone metastasis compared with both lung metastasis and liver metastasis. A total of three DElncRNAs in bone metastasis compared with both lung metastasis and liver metastasis were obtained. A total of seven DElncRNA-nearby-targeted DEmRNA pairs and 15 DElncRNA-nearby-targeted DEmRNA pairs in group of bone metastasis vs lung metastasis and bone metastasis vs liver metastasis, were detected, respectively. Four cis LncRNA-mRNA interaction pairs were identified, which are LOC641518-LEF1, FLJ35024-Very Low Density Lipoprotein Receptor (VLDLR), LOC285972-Retinoic Acid Receptor Responder 2 (RARRES2) and LOC254896-TNF receptor superfamily member 10c (TNFRSF10C). qRT-PCR using clinical samples from our hospital confirms the bioinformatics prediction. siRNA knocking down LOC641518 down-regulates LEF1 mRNA expression, and reduces the migration and invasion capability of breast cancer cells. CONCLUSIONS: We concluded that four LncRNA-mRNA pairs, including LOC641518-LEF1, may play a central role in breast cancer bone metastasis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02068-7. BioMed Central 2021-07-13 /pmc/articles/PMC8276423/ /pubmed/34256750 http://dx.doi.org/10.1186/s12935-021-02068-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Zhang, Yu
Huang, Xiaofeng
Liu, Jin
Chen, Guo
Liu, Chengjun
Zhang, Sen
Li, Jiaxin
New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis
title New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis
title_full New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis
title_fullStr New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis
title_full_unstemmed New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis
title_short New insight into long non-coding RNAs associated with bone metastasis of breast cancer based on an integrated analysis
title_sort new insight into long non-coding rnas associated with bone metastasis of breast cancer based on an integrated analysis
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276423/
https://www.ncbi.nlm.nih.gov/pubmed/34256750
http://dx.doi.org/10.1186/s12935-021-02068-7
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