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miR‐370 modulates insulin receptor substrate‐1 expression and inhibits the tumor phenotypes of oral carcinoma
Author(s) -
Chang KW,
Chu TH,
Gong NR,
Chiang WF,
Yang CC,
Liu CJ,
Wu CH,
Lin SC
Publication year - 2013
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12046
Subject(s) - gene knockdown , carcinogenesis , cancer research , irs1 , pi3k/akt/mtor pathway , cell growth , rna interference , protein kinase b , biology , chemistry , cancer , insulin , medicine , endocrinology , insulin receptor , signal transduction , cell culture , microbiology and biotechnology , rna , insulin resistance , gene , genetics , biochemistry
Background Micro RNA s play important roles in carcinogenesis. A preliminary screening study suggested that down‐regulation of mi R ‐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 mi R ‐370 and IRS ‐1, and their functional roles in OSCC pathogenesis are unclear. Materials and Methods Primary OSCC specimens were examined for mi R ‐370 expression. Exogenous expression of mi R ‐370 was established using both stable subclones and transient expression, and these were used to gain insights into mi R ‐370 's functions in OSCC cells. Knockdown of mi R ‐370 and IRS ‐1 was also carried out in OSCC cells using a small interference oligonucleotide approach. Results Squamous cell carcinoma tissues with perineural invasion had lowered mi R ‐370 expression compared with contrasting OSCC . OSCC cells also exhibited lower mi R ‐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. Conclusion This study concludes that miR‐370 is able to target IRS ‐1 for oral tumorigenesis.