title: HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer.
abstract: The oncoprotein hepatitis B X-interacting protein (HBXIP) results in the dysregulation of lipid metabolism to enhance the development of breast cancer. Acyl-CoA synthetase long-chain family member 1 (ACSL1) is required for thioesterification of long-chain fatty acids into their acyl-CoA derivatives. In this study, we present a hypothesis that HBXIP might be involved in the regulation of ACSL1 in breast cancer. Interestingly, we found that the overexpression of HBXIP was able to up-regulate ACSL1 at the levels of mRNA and protein in a dose-dependent manner in breast cancer cells. Conversely, silencing of HBXIP led to the opposite results. Mechanistically, HBXIP as a coactivator interacted with transcriptional factor Sp1 through binding to the promoter of ACSL1 by ChIP assays analysis, leading to the transcription of ACSL1 in breast cancer cells. Immunohistochemistry staining revealed that the positive rate of ACSL1 was 71.4% (35/49) in clinical breast cancer tissues, HBXIP 79.6% (39/49), in which the positive rate of ACSL1 was 76.9% (30/39) in the HBXIP-positive specimens. But, few positive rate of ACSL1 10% (1/10) was observed in normal breast tissues. The mRNA levels of ACSL1 were significantly higher in clinical breast cancer tissues than those in their corresponding peritumor tissues. The mRNA levels of ACSL1 were positively associated with those of HBXIP in clinical breast cancer tissues. Thus, we conclude that the oncoprotein HBXIP is able to up-regulate ACSL1 through activating the transcriptional factor Sp1 in breast cancer.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Fabao
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Baodi
authors.initials: B
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: yelihong@nankai.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D003066:Coenzyme A Ligases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C110719:LAMTOR5 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D003066:Coenzyme A Ligases; C583414:ACSL1 protein, human
keywords: ACSL1; Breast cancer; HBXIP; Sp1