Contribute equally to this work.
miR-370 modulates insulin receptor substrate-1 expression and inhibits the tumor phenotypes of oral carcinoma
Article first published online: 12 DEC 2012
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 19, Issue 6, pages 611–619, September 2013
How to Cite
Oral Diseases (2013) 19, 611–619
- Issue published online: 10 JUL 2013
- Article first published online: 12 DEC 2012
- Accepted manuscript online: 24 NOV 2012 06:08AM EST
- Manuscript Accepted: 8 NOV 2012
- Manuscript Revised: 25 OCT 2012
- Manuscript Received: 20 JUL 2012
- National Science Council
- miR-370 ;
MicroRNAs play important roles in carcinogenesis. A preliminary screening study suggested that down-regulation of miR-370 occurs in oral squamous cell carcinoma (OSCC) tissue. Insulin receptor substratre-1 (IRS-1) is the substrate of insulin-like growth factor receptor (IGFR), which modulates AKT/mTOR activation in malignancies. The relationship between miR-370 and IRS-1, and their functional roles in OSCC pathogenesis are unclear.
Materials and Methods
Primary OSCC specimens were examined for miR-370 expression. Exogenous expression of miR-370 was established using both stable subclones and transient expression, and these were used to gain insights into miR-370's functions in OSCC cells. Knockdown of miR-370 and IRS-1 was also carried out in OSCC cells using a small interference oligonucleotide approach.
Squamous cell carcinoma tissues with perineural invasion had lowered miR-370 expression compared with contrasting OSCC. OSCC cells also exhibited lower miR-370 expression than normal oral keratinocytes, and this can be reversed by treatment with 5-aza-2′-deoxycytidine. Exogenous miR-370 expression decreases the migration and anchorage-independent growth of OSCC cells, which implies a suppressor role for miR-370. The enhancement of anchorage-independent growth of OSCC cells through miR-370 inhibiting can be reduced by knockdown of IRS-1 expression.
This study concludes that miR-370 is able to target IRS-1 for oral tumorigenesis.