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

Full 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.

Author information

Author/s: Edmonds, Mick D (MD); Hurst, Douglas R (DR); Vaidya, Kedar S (KS); Stafford, Lewis J (LJ); Chen, Dongquan (D); Welch, Danny R (DR);

Affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.

Grants: CA13148 (Agency:NCI NIH HHS) ; CA87728 (Agency:NCI NIH HHS) ; F32CA113037 (Agency:NCI NIH HHS) ; UL1RR025777 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1778-85

Dates: Created 2009/08/26; Completed 2009/09/21; Revised 2009/09/25;

PMID: 19585508, status: MEDLINE (last retrieval date: 9/28/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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