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, Wei Gu

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15690-15702
Number of pages13
JournalOncotarget
Volume7
Issue number13
DOIs
StatePublished - Mar 29 2016

Fingerprint

Breast Neoplasms
Neoplasm Metastasis
Messenger RNA
Growth
Heterografts
Insulin-Like Growth Factor II
Cyclooxygenase 2
Microarray Analysis
Neoplasms
Cell Proliferation
Phenotype
Gene Expression
Lung
Proteins

Keywords

  • Breast cancer growth and metastasis
  • Gene expression
  • Post-transcriptional regulation of mrnas
  • Rna-binding protein
  • Zbp1/imp1

ASJC Scopus subject areas

  • Oncology

Cite this

Wang, G., Huang, Z., Liu, X., Huang, W., Chen, S., Zhou, Y., ... Gu, W. (2016). IMP1 suppresses breast tumor growth and metastasis through the regulation of its target mRNAs. Oncotarget, 7(13), 15690-15702. https://doi.org/10.18632/oncotarget.7464

IMP1 suppresses breast tumor growth and metastasis through the regulation of its target mRNAs. / Wang, Guangli; Huang, Zhenqiang; Liu, Xin; Huang, Wenhe; Chen, Shaoying; Zhou, Yanchun; Li, Deling; Singer, Robert H.; Gu, Wei.

In: Oncotarget, Vol. 7, No. 13, 29.03.2016, p. 15690-15702.

Research output: Contribution to journalArticle

Wang, G, Huang, Z, Liu, X, Huang, W, Chen, S, Zhou, Y, Li, D, Singer, RH & Gu, W 2016, 'IMP1 suppresses breast tumor growth and metastasis through the regulation of its target mRNAs', Oncotarget, vol. 7, no. 13, pp. 15690-15702. https://doi.org/10.18632/oncotarget.7464
Wang, Guangli ; Huang, Zhenqiang ; Liu, Xin ; Huang, Wenhe ; Chen, Shaoying ; Zhou, Yanchun ; Li, Deling ; Singer, Robert H. ; Gu, Wei. / IMP1 suppresses breast tumor growth and metastasis through the regulation of its target mRNAs. In: Oncotarget. 2016 ; Vol. 7, No. 13. pp. 15690-15702.
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