HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-MycHBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc
PUBLISHED: 2016-02-18  801 total views, 2 today

Yinghui Li1Zhen Wang1Hui Shi1Hang Li1Leilei Li1Runping Fang1,Xiaoli Cai1Bowen Liu1Xiaodong Zhang2,*, and Lihong Ye1,*

Author Affiliations

1State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, P.R. China.
2State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin, P.R. China.

*Corresponding Authors:
Lihong Ye, Nankai University, 94 Weijin Road, Tianjin 300071, China. Phone: 86-22-23501385; Fax: 86-22-23501385; E-mail: yelihong@nankai.edu.cn; and Xiaodong Zhang,zhangxd@nankai.edu.cn

Abstract

c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc–mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc–enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis. Cancer Res; 76(2); 293–304. ©2015 AACR.

Disclaimer: Only abstract of articles from non-members were published. This page aims to promote Chinese scientific research. There is no conflicts of interest with any journals reserved the copyright. For more please contact the author.


Author
Dr. Ye Lihong
+ Author Profile

Dr. Ye Lihong

Director of Protein Biochemistry Laboratory and Distinguished professorof Nankai University

Email: yelihong@nankai.edu.cn


Expertise

  • Molecularmechanisms of tumorigenesis, tumor growth, tumor metastasis.

  • Screening ofanticancer drugs

 

Research Project

  • Human breastcancer cell line with High metastatic tendency and its establishing method.

  • Human hepatocellularcarcinoma Metastasis subclone cell line and its established method.

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