Breast cancer metastasis suppressor 1 coordinately regulates metastasis-associated microRNA expression

Authors

  • Mick D. Edmonds,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
    Search for more papers by this author
  • Douglas R. Hurst,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
    Search for more papers by this author
  • Kedar S. Vaidya,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
    Search for more papers by this author
  • Lewis J. Stafford,

    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
    Search for more papers by this author
  • Dongquan Chen,

    1. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
    2. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
    Search for more papers by this author
  • Danny R. Welch

    Corresponding author
    1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL
    2. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
    3. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
    4. Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL
    5. Department of Pharmacology/Toxicology, University of Alabama at Birmingham, Birmingham, AL
    • Department of Pathology, 1670 University Blvd. Room VH-G019, Birmingham, AL 35294-0019, USA
    Search for more papers by this author
    • Fax: +1-205-975-1126.


  • Conflicts of interest: The authors declare no conflicts of interest.

Abstract

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple tumor types without blocking tumorigenesis. BRMS1 forms complexes with SIN3, histone deacetylases and selected transcription factors that modify metastasis-associated gene expression (e.g., EGFR, OPN, PI4P5K1A, PLAU). microRNA (miRNA) are a recently discovered class of regulatory, noncoding RNA, some of which are involved in neoplastic progression. Based on these data, we hypothesized that BRMS1 may also exert some of its antimetastatic effects by regulating miRNA expression. MicroRNA arrays were done comparing small RNAs that were purified from metastatic MDA-MB-231 and MDA-MB-435 and their nonmetastatic BRMS1-transfected counterparts. miRNA expression changed by BRMS1 were validated using SYBR Green RT-PCR. BRMS1 decreased metastasis-promoting (miR-10b, -373 and -520c) miRNA, with corresponding reduction of their downstream targets (e.g., RhoC which is downstream of miR-10b). Concurrently, BRMS1 increased expression of metastasis suppressing miRNA (miR-146a, -146b and -335). Collectively, these data show that BRMS1 coordinately regulates expression of multiple metastasis-associated miRNA and suggests that recruitment of BRMS1-containing SIN3:HDAC complexes to, as yet undefined, miRNA promoters might be involved in the regulation of cancer metastasis. © 2009 UICC

Ancillary