Oncotarget

Research Papers:

IMP1 suppresses breast tumor growth and metastasis through the regulation of its target mRNAs

Guangli Wang, Zhenqiang Huang, Xin Liu, Wenhe Huang, Shaoying Chen, Yanchun Zhou, Deling Li, Robert H. Singer and Wei Gu _

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Oncotarget. 2016; 7:15690-15702. https://doi.org/10.18632/oncotarget.7464

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Abstract

Guangli Wang1,*, Zhenqiang Huang1,*, Xin Liu1, Wenhe Huang2, Shaoying Chen1, Yanchun Zhou1, Deling Li1, Robert H. Singer3, Wei Gu1

1Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, 515031, China

2Tumor Hospital, Shantou University Medical College, Shantou, Guangdong Province, 515031, China

3Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA

*These authors have contributed equally to this work

Correspondence to:

Wei Gu, e-mail: weigu1@yahoo.com

Keywords: breast cancer growth and metastasis, gene expression, post-transcriptional regulation of mRNAs, RNA-binding protein, ZBP1/IMP1

Received: October 25, 2015     Accepted: February 05, 2016     Published: February 17, 2016

ABSTRACT

We have previously reported the ability of IMP1 in inhibiting proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized a mouse xenograft model to further investigate the function of IMP1 in breast tumor progression and its underlying mechanism. We demonstrated that IMP1 expression significantly suppressed the growth of MDA231 cell-derived xenograft tumors and subsequent lung metastasis. Microarray analyses and differential gene expression identified handful mRNAs, many of which were involved in breast tumor-growth and metastasis. Further studies revealed that these mRNAs were directly interacted with the KH34 domain of IMP1 and this interaction post-transcriptionally regulated their corresponding protein expression. Either deletion of the KH34 domain of IMP1 or alteration of the expression of IMP1-bound mRNAs affected cell proliferation and tumor growth, producing the same phenotypes as IMP1 knockdown. Correlation of increased IMP1 expression with the reduced levels of its bound mRNAs, such as PTGS2, GDF15 and IGF-2 transcripts, was also observed in human breast tumors. Our studies provide insights into a molecular mechanism that the positive function of IMP1 to inhibit breast tumor growth and metastasis could be through the regulation of its target mRNAs.


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