title: MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling.
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.
authors: Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, M4N 3M5, Canada.
authors: William W
authors: WW
authors: Du
authors: Ling
authors: L
authors: Fang
authors: Minhui
authors: M
authors: Li
authors: Xiangling
authors: X
authors: Yang
authors: Yaoyun
authors: Y
authors: Liang
authors: Chun
authors: C
authors: Peng
authors: Wei
authors: W
authors: Qian
authors: Yunxia Q
authors: YQ
authors: O'Malley
authors: Ryan W
authors: RW
authors: Askeland
authors: Sonia L
authors: SL
authors: Sugg
authors: Jun
authors: J
authors: Qian
authors: Jiang
authors: J
authors: Lin
authors: Zide
authors: Z
authors: Jiang
authors: Albert J
authors: AJ
authors: Yee
authors: Michael
authors: M
authors: Sefton
authors: Zhaoqun
authors: Z
authors: Deng
authors: Sze Wan
authors: SW
authors: Shan
authors: Chia-Hui
authors: CH
authors: Wang
authors: Burton B
authors: BB
authors: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C447615:PTPN9 protein, human; C516772:PTPRF protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Metastasis; MicroRNA; Tumor invasion; miR-24; pEGFR