Microrna mir-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling

William W. Du, Ling Fang, Minhui Li, Xiangling Yang, Yaoyun Liang, Chun Peng, Wei Qian, Yunxia Q. O'Malley, Ryan W. Askeland, Sonia L. Sugg, Jun Qian, Jiang Lin, Zide Jiang, Albert J. Yee, Michael Sefton, Zhaoqun Deng, Sze Wan Shan, Chia Hui Wang, Burton B. Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

115 Citations (Scopus)

Abstract

MicroRNAs are known to play regulatory roles in gene expression associated with cancer development. We analyzed levels of the microRNA miR-24 in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in benign breast tissues. We generated constructs expressing miR-24 and studied its functions using both in vitro and in vivo techniques. We found that the ectopic expression of miR-24 promoted breast cancer cell invasion and migration. In vivo experiments in mice indicated that the expression of miR-24 enhanced tumor growth, invasion into local tissues, metastasis to lung tissues and decreased overall mouse survival. In the miR-24-expressing cells and tumors, EGFR was highly phosphorylated, whereas expression of the phosphatases tyrosine-protein phosphatase non-receptor type 9 (PTPN9) and receptor-type tyrosine-protein phosphatase F (PTPRF) were repressed. We confirmed that miR-24 could directly target both PTPN9 and PTPRF. Consistent with this, we found that the levels of phosphorylated epidermal growth factor receptor (pEGFR) were higher whereas the levels of PTPN9 and PTPRF were lower in the patients with metastatic breast carcinoma. Ectopic expression of PTPN9 and PTPRF decreased pEGFR levels, cell invasion, migration and tumor metastasis. Furthermore, we found that MMP2, MMP11, pErk, and ADAM15 were upregulated, whereas TIMP2 was downregulated; all of which supported the roles of miR-24 in tumor invasion and metastasis. Our results suggest that miR-24 plays a key role in breast cancer invasion and metastasis. miR-24 could potentially be a target for cancer intervention.

Original languageEnglish
Pages (from-to)1440-1453
Number of pages14
JournalJournal of Cell Science
Volume126
Issue number6
DOIs
Publication statusPublished - 15 Mar 2013
Externally publishedYes

Keywords

  • Metastasis
  • Microrna
  • Mir-24
  • PEGFR
  • Tumor invasion

ASJC Scopus subject areas

  • Cell Biology

Cite this