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

// Guangli Wang 1, * , Zhenqiang Huang 1, * , Xin Liu 1 , Wenhe Huang 2 , Shaoying Chen 1 , Yanchun Zhou 1 , Deling Li 1 , Robert H. Singer 3 , Wei Gu 1 1 Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, 515031, China 2 Tumor Hospital, Shantou University Medical College, Shantou, Guangdong Province, 515031, China 3 Department 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.