LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications

Abstract Long-noncoding RNAs (lncRNAs) have been shown to participate in oncogenesis across a variety of cancers and may represent novel therapeutic targets. However, little is known about the role of lncRNAs in basal-like breast cancer (BLBC), the aggressive form of breast cancer with no molecularl...

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Autores principales:	Yoo Jane Han, Sonja M. Boatman, Jing Zhang, Xinxin C. Du, Albert C. Yeh, Yonglan Zheng, Jeffrey Mueller, Olufunmilayo I. Olopade
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Basal-like Breast Cancer (BLBC) lncRNAs BLBC Tumors Aggressive BLBC BLBC Cell Lines Medicine R Science Q
Acceso en línea:	https://doaj.org/article/283a202ccf0345a989c5f5b292d3ff4a
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spelling	oai:doaj.org-article:283a202ccf0345a989c5f5b292d3ff4a2021-12-02T15:08:29ZLncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications10.1038/s41598-018-33629-y2045-2322https://doaj.org/article/283a202ccf0345a989c5f5b292d3ff4a2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33629-yhttps://doaj.org/toc/2045-2322Abstract Long-noncoding RNAs (lncRNAs) have been shown to participate in oncogenesis across a variety of cancers and may represent novel therapeutic targets. However, little is known about the role of lncRNAs in basal-like breast cancer (BLBC), the aggressive form of breast cancer with no molecularly defined therapeutic target. To examine whether altered lncRNA expression contributes to the aggressive phenotype characteristic of BLBC, we performed a comparative analysis of BLBC versus non-BLBC using microarray profiling and RNA sequencing of primary breast cancer. We identified RP11-19E11.1 as a significantly up-regulated lncRNA in BLBC tumors and named it Basal-Like breast cancer Associated Transcript 1 (BLAT1). Analysis of pan-cancer datasets showed the highest expression of BLAT1 in BLBC tumors compared to all other cancers. Depletion of BLAT1 in breast cancer cells led to significantly increased apoptosis, partly because of accumulation of DNA damage. Mechanistically, BLAT1 expression is regulated at the epigenetic level via DNA methylation at CpG islands in the promoter. Concordantly, patients harboring tumors with BLAT1 hypomethylation showed decreased overall survival. Our results suggest that increased expression of BLAT1 via CpG site hypomethylation may contribute to the aggressive phenotype of BLBC, raising a possibility of new biomarkers for prognosis of aggressive BLBC tumors.Yoo Jane HanSonja M. BoatmanJing ZhangXinxin C. DuAlbert C. YehYonglan ZhengJeffrey MuellerOlufunmilayo I. OlopadeNature PortfolioarticleBasal-like Breast Cancer (BLBC)lncRNAsBLBC TumorsAggressive BLBCBLBC Cell LinesMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Basal-like Breast Cancer (BLBC) lncRNAs BLBC Tumors Aggressive BLBC BLBC Cell Lines Medicine R Science Q
spellingShingle	Basal-like Breast Cancer (BLBC) lncRNAs BLBC Tumors Aggressive BLBC BLBC Cell Lines Medicine R Science Q Yoo Jane Han Sonja M. Boatman Jing Zhang Xinxin C. Du Albert C. Yeh Yonglan Zheng Jeffrey Mueller Olufunmilayo I. Olopade LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
description	Abstract Long-noncoding RNAs (lncRNAs) have been shown to participate in oncogenesis across a variety of cancers and may represent novel therapeutic targets. However, little is known about the role of lncRNAs in basal-like breast cancer (BLBC), the aggressive form of breast cancer with no molecularly defined therapeutic target. To examine whether altered lncRNA expression contributes to the aggressive phenotype characteristic of BLBC, we performed a comparative analysis of BLBC versus non-BLBC using microarray profiling and RNA sequencing of primary breast cancer. We identified RP11-19E11.1 as a significantly up-regulated lncRNA in BLBC tumors and named it Basal-Like breast cancer Associated Transcript 1 (BLAT1). Analysis of pan-cancer datasets showed the highest expression of BLAT1 in BLBC tumors compared to all other cancers. Depletion of BLAT1 in breast cancer cells led to significantly increased apoptosis, partly because of accumulation of DNA damage. Mechanistically, BLAT1 expression is regulated at the epigenetic level via DNA methylation at CpG islands in the promoter. Concordantly, patients harboring tumors with BLAT1 hypomethylation showed decreased overall survival. Our results suggest that increased expression of BLAT1 via CpG site hypomethylation may contribute to the aggressive phenotype of BLBC, raising a possibility of new biomarkers for prognosis of aggressive BLBC tumors.
format	article
author	Yoo Jane Han Sonja M. Boatman Jing Zhang Xinxin C. Du Albert C. Yeh Yonglan Zheng Jeffrey Mueller Olufunmilayo I. Olopade
author_facet	Yoo Jane Han Sonja M. Boatman Jing Zhang Xinxin C. Du Albert C. Yeh Yonglan Zheng Jeffrey Mueller Olufunmilayo I. Olopade
author_sort	Yoo Jane Han
title	LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
title_short	LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
title_full	LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
title_fullStr	LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
title_full_unstemmed	LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications
title_sort	lncrna blat1 is upregulated in basal-like breast cancer through epigenetic modifications
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/283a202ccf0345a989c5f5b292d3ff4a
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LncRNA BLAT1 is Upregulated in Basal-like Breast Cancer through Epigenetic Modifications

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