Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells

Hongpeng He; Zhaoqiang Wei; Fu Du; Chao Meng; Deliang Zheng; Yongwei Lai; Hailin Yao; Hao Zhou; Nan Wang; Xue-Gang Luo; Wenjian Ma; Tong-Cun Zhang

doi:10.1016/j.cellsig.2017.01.003

Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells

Cell Signal. 2017 Feb:31:87-95. doi: 10.1016/j.cellsig.2017.01.003. Epub 2017 Jan 7.

Authors

Hongpeng He¹, Zhaoqiang Wei¹, Fu Du¹, Chao Meng¹, Deliang Zheng¹, Yongwei Lai¹, Hailin Yao¹, Hao Zhou¹, Nan Wang¹, Xue-Gang Luo¹, Wenjian Ma¹, Tong-Cun Zhang²

Affiliations

¹ Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
² Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.; College of Life Sciences, Wuhan University of Science and Technology, Wuhan 430081, PR China.. Electronic address: tony@tust.edu.cn.

PMID: 28069441
DOI: 10.1016/j.cellsig.2017.01.003

Abstract

HOTAIR is a long non-coding RNA highly expressed in cancer tissues and is a negative prognostic factor, whereas the mechanism by which HOTAIR expression is upregulated in cancers remains elusive. In the present study, the regulation of HOTAIR transcription was investigated in breast cancer cells MCF7 and T47D. We found that, when the RhoC-ROCK signaling was disturbed by specific siRNAs or chemical inhibitors, the expression of HOTAIR would be down-regulated. Further, MRTF-A and SRF were found to affect HOTAIR expression. HOTAIR promoter activity was demonstrated to be regulated by the RhoC-MRTF-A-SRF signaling in a CArG-box-dependent manner. Moreover, MRTF-A was identified to physically interact with HOTAIR promoter, and RNA polymerase II association on HOTAIR promoter was enhanced by MRTF-A overexpression. Taken together, our results suggest that HOTAIR is regulated by the RhoC-MRTF-A-SRF signaling pathway in breast cancer cells.

Keywords: Breast cancer; HOTAIR; MRTF-A; Rho-signaling; Transcription.

MeSH terms

Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Nucleus / metabolism
Female
Gene Expression Regulation, Neoplastic*
Humans
Models, Biological
Promoter Regions, Genetic
Protein Binding / genetics
RNA Polymerase II / metabolism
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Serum Response Factor / metabolism*
Signal Transduction*
Trans-Activators / metabolism*
Transcription, Genetic*
rho-Associated Kinases / metabolism
rhoC GTP-Binding Protein / metabolism*

Substances

HOTAIR long untranslated RNA, human
MRTFA protein, human
RNA, Long Noncoding
Serum Response Factor
Trans-Activators
rho-Associated Kinases
RNA Polymerase II
RHOC protein, human
rhoC GTP-Binding Protein