miR-370 modulates insulin receptor substrate-1 expression and inhibits the tumor phenotypes of oral carcinoma

Authors

  • K-W Chang,

    1. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    2. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
    3. Department of Stomatology, Veterans General Hospital, Taipei, Taiwan
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    • Contribute equally to this work.
  • T-H Chu,

    1. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
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    • Contribute equally to this work.
  • N-R Gong,

    1. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
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  • W-F Chiang,

    1. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    2. Department of Dentistry, Chi-Mei Medical Center, Tainan, Taiwan
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  • C-C Yang,

    1. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    2. Department of Stomatology, Veterans General Hospital, Taipei, Taiwan
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  • C-J Liu,

    1. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    2. Department of Dentistry, MacKay Memorial Hospital, Taipei, Taiwan
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  • C-H Wu,

    1. Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
    2. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
    3. Department of Stomatology, Veterans General Hospital, Taipei, Taiwan
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  • S-C Lin

    Corresponding author
    1. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
    2. Department of Stomatology, Veterans General Hospital, Taipei, Taiwan
    • Department of Dentistry, National Yang-Ming University, Taipei, Taiwan
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Correspondence: Shu-Chun Lin, PhD, Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Beitou, 112 Taipei, Taiwan. Tel: +8862 28267272, Fax: +8862 28264053, E-mail: sclin@ym.edu.tw

Abstract

Background

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.

Results

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.

Conclusion

This study concludes that miR-370 is able to target IRS-1 for oral tumorigenesis.

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