Wan Li1,2, Xiangjin Zheng1,2, Liwen Ren1,2, Weiqi Fu1,2, Jinyi Liu1,2, Jun Xv3, Shiwei Liu3, Jinhua Wang1,2,4, Guanhua Du1,2. 1. The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. 2. Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. 3. Department of Endocrinology, Shanxi DAYI Hospital, Shanxi Medical University, Taiyuan 030002, China. 4. Department of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI) at Providence Saint John's Health Center, Santa Monica, CA, USA.
Abstract
BACKGROUND: Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear. METHODS: In silico analysis of the expression of GD3s in TNBC was conducted using The Cancer Genome Atlas (TCGA) and Oncomine databases. The proliferation of breast cancer cells was measured by MTT assay, colony formation by the soft agar method, and migration and invasion using Boyden chamber inserts. The methylation level of the gene encoding GD3s, ST8SIA1, in specimens was assessed by qMS-PCR and in silico using the UCSC gene browser. Protein expression was examined via immunohistochemistry (IHC), qRT-PCR and Western immunoblotting. RESULTS: In silico analysis showed a higher GD3s expression in ER- than ER+ breast cancers and GD3s was also highly expressed in TNBC compared to other types of breast cancers. The elevated GD3s expression in TNBC cells and tissues was associated with hypomethylation of the ST8SIA1 gene. Overexpression of GD3s in human breast cancer cells increased their proliferation, migration, invasion and colony formation ability. GD3s expression in breast cancers was closely associated with relapse-free survival (RFS) and overall survival (OS). CONCLUSIONS: In summary, these results suggest that GD3s may be a potential biomarker and drug target in treatment of TNBC. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Breast cancer remains a major health problem in the world. Triple-negative breast cancer (TNBC) is an aggressive subtype with very poor prognosis. Up to now, the mechanism behind TNBC's activity is still unclear and no candidate drug target has been identified. Thus, it is of critical importance to elucidate the pathways in TNBC and identify the relevant biomarkers. Recent studies showed that ganglioside D3 synthase (GD3s) played a very important role in development of cancers. However, the physiological functions and associated pathways of GD3s in TNBC are still unclear. METHODS: In silico analysis of the expression of GD3s in TNBC was conducted using The Cancer Genome Atlas (TCGA) and Oncomine databases. The proliferation of breast cancer cells was measured by MTT assay, colony formation by the soft agar method, and migration and invasion using Boyden chamber inserts. The methylation level of the gene encoding GD3s, ST8SIA1, in specimens was assessed by qMS-PCR and in silico using the UCSC gene browser. Protein expression was examined via immunohistochemistry (IHC), qRT-PCR and Western immunoblotting. RESULTS: In silico analysis showed a higher GD3s expression in ER- than ER+ breast cancers and GD3s was also highly expressed in TNBC compared to other types of breast cancers. The elevated GD3s expression in TNBC cells and tissues was associated with hypomethylation of the ST8SIA1 gene. Overexpression of GD3s in human breast cancer cells increased their proliferation, migration, invasion and colony formation ability. GD3s expression in breast cancers was closely associated with relapse-free survival (RFS) and overall survival (OS). CONCLUSIONS: In summary, these results suggest that GD3s may be a potential biomarker and drug target in treatment of TNBC. 2019 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Ganglioside D3 synthase (GD3s); biomarker; methylation; prognosis; triple-negative breast cancer (TNBC)
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