miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α

The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffect...

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Main Authors:	Xing, Fei, Sharma, Sambad, Liu, Yin, Mo, Yin-Yuan, Wu, Kerui, Zhang, Ying-Yu, Pochampally, Radhika, Martinez, Luis A, Lo, Hui-wen, Watabe, Kounosuke
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530094/

id	pubmed-4530094
recordtype	oai_dc
spelling	pubmed-45300942016-03-10 miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α Xing, Fei Sharma, Sambad Liu, Yin Mo, Yin-Yuan Wu, Kerui Zhang, Ying-Yu Pochampally, Radhika Martinez, Luis A Lo, Hui-wen Watabe, Kounosuke Article The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, while the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating two genes essential for brain invasion, RhoC and TNFα that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNFα and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 plays a critical role in brain metastasis of breast cancer by modulating the RhoC-TNFα network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis. 2015-02-09 2015-09-10 /pmc/articles/PMC4530094/ /pubmed/25659578 http://dx.doi.org/10.1038/onc.2014.412 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Xing, Fei Sharma, Sambad Liu, Yin Mo, Yin-Yuan Wu, Kerui Zhang, Ying-Yu Pochampally, Radhika Martinez, Luis A Lo, Hui-wen Watabe, Kounosuke
spellingShingle	Xing, Fei Sharma, Sambad Liu, Yin Mo, Yin-Yuan Wu, Kerui Zhang, Ying-Yu Pochampally, Radhika Martinez, Luis A Lo, Hui-wen Watabe, Kounosuke miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α
author_facet	Xing, Fei Sharma, Sambad Liu, Yin Mo, Yin-Yuan Wu, Kerui Zhang, Ying-Yu Pochampally, Radhika Martinez, Luis A Lo, Hui-wen Watabe, Kounosuke
author_sort	Xing, Fei
title	miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α
title_short	miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α
title_full	miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α
title_fullStr	miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α
title_full_unstemmed	miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α
title_sort	mir-509 suppresses brain metastasis of breast cancer cells by modulating rhoc and tnf α
description	The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, while the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating two genes essential for brain invasion, RhoC and TNFα that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNFα and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 plays a critical role in brain metastasis of breast cancer by modulating the RhoC-TNFα network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530094/
_version_	1613257349527502848

miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α

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