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

doi:10.1242/jcs.118299

Back

MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling

Journal article

Peer reviewed

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, …

Journal of cell science, Vol.126(Pt 6), pp.1440-1453

03/15/2013

DOI: 10.1242/jcs.118299

PMID: 23418360

View Online

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.

Neoplasm Transplantation

Receptor, Epidermal Growth Factor - genetics

Humans

Transgenes - genetics

Epidermal Growth Factor - metabolism

MicroRNAs - metabolism

Signal Transduction - genetics

Neoplasm Metastasis

Receptor, Epidermal Growth Factor - metabolism

Animals

Breast Neoplasms - genetics

Breast Neoplasms - pathology

Protein Tyrosine Phosphatases, Non-Receptor - genetics

Protein Tyrosine Phosphatases, Non-Receptor - metabolism

Receptor-Like Protein Tyrosine Phosphatases, Class 2 - metabolism

HEK293 Cells

Female

Mice

Mice, Inbred BALB C

MicroRNAs - genetics

Receptor-Like Protein Tyrosine Phosphatases, Class 2 - genetics

Cell Growth Processes - genetics

Neoplasm Invasiveness - genetics

Gene Expression Regulation, Neoplastic - genetics

Details

Title: Subtitle: MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling
Creators: William W Du - Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N 3M5, Canada
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
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.126(Pt 6), pp.1440-1453
DOI: 10.1242/jcs.118299
PMID: 23418360
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Grant note: MOP-102635 / Canadian Institutes of Health Research MOP-89931 / Canadian Institutes of Health Research MOP-111171 / Canadian Institutes of Health Research
Language: English
Date published: 03/15/2013
Academic Unit: Stead Family Department of Pediatrics; Surgery; Gastroenterology, Hepatology, Pancreatology, and Nutrition
Record Identifier: 9984051750302771

Metrics

19 Record Views

133 Times Cited - Web of Science

See more details