title: The oncoprotein HBXIP upregulates Lin28B via activating TF II D to promote proliferation of breast cancer cells.
abstract: Hepatitis B X-interacting protein (HBXIP) is a novel oncoprotein and plays a key role in the development of breast cancer. However, its mechanisms of action are poorly understood. Lin28B functions as an oncogene in a variety of human cancers. In our study, we report that HBXIP acts with its partner Lin28B to contribute to carcinogenesis. Our data showed that the expression levels of HBXIP were significantly positively correlated with those of Lin28B in clinical breast cancer tissues. Then, we found that HBXIP was able to upregulate Lin28B in breast cancer MCF-7 cells. Chromatin immunoprecipitation assay (ChIP) and electrophoretic mobility shift assay (EMSA) revealed that HBXIP occupied the promoter region (-1199/-1073 nt) of Lin28B. Importantly, co-immunoprecipitation (Co-IP) and GST pull-down assay validated that HBXIP directly bound to the TATA-binding protein (TBP), a basal subunit of transcription factor TF II D complex. In addition, we discovered that Lin28B could block the downregulation of HBXIP via suppressing miR-520b which directly targeted HBXIP mRNA in the cells. In function, we demonstrated that HBXIP enhanced the proliferation of breast cancer cells through Lin28B in vitro and in vivo. Thus, we conclude that the oncoprotein HBXIP as a co-activator of TF II D transactivates Lin28B promoter via directly binding to TBP to upregulate the expression of Lin28B in promotion of proliferation of breast cancer cells, in which Lin28B maintains the high level of HBXIP through suppressing miR-520b in a feedback manner. Therapeutically, HBXIP may serve as a target of breast cancer.
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, 300071, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Bai
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D035362:Transcription Factor TFIID / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110719:LAMTOR5 protein, human; C000715187:Lin28A protein, human; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D035362:Transcription Factor TFIID
keywords: HBXIP; Lin28B; TF II D; carcinogenesis; miRNA-520b