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

Breast cancer metastasis suppressor 1 coordinately regulates metastasis-associated microRNA expression.
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DOI:
10.1002/ijc.24616
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发表时间:
2009-10-15
影响因子:
6.4
通讯作者:
Welch DR
Welch DR
中科院分区:
医学1区
文献类型:
--
作者:
Edmonds MD;Hurst DR;Vaidya KS;Stafford LJ;Chen D;Welch DR

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乳腺癌转移抑制因子1(BRMS 1)抑制多种肿瘤类型的转移,但不阻断肿瘤发生。BRMS 1与SIN 3、组蛋白脱乙酰酶和选择的修饰转移相关基因表达的转录因子(例如,EGFR、OPN、PI4P5K1A、PLAU)。微小RNA(microRNA,miRNA)是近年来发现的一类具有调控作用的非编码RNA,其中一些与肿瘤的进展有关。基于这些数据,我们假设BRMS 1也可能通过调节miRNA表达发挥其抗转移作用。进行微RNA阵列,比较从转移性MDA-MB-231和MDA-MB-435及其非转移性BRMS 1转染的对应物中纯化的小RNA。采用SYBR绿色RT-PCR验证BRMS 1改变的miRNA表达。BRMS 1减少了促进转移的(miR-10 b、-373和-520c)miRNA,相应地减少了它们的下游靶标(例如,RhoC,其位于miR-10 b的下游)。同时,BRMS 1增加转移抑制miRNA(miR-146 a、-146 b和-335)的表达。总的来说,这些数据表明,BRMS 1协调调节多种转移相关的miRNA的表达,并表明含有BRMS 1的SIN 3:HDAC复合物募集到尚未确定的miRNA启动子可能参与调节癌症转移。
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. Micro-RNA arrays were done comparing small RNAs that were purified from metastatic MDA-MB-231 and MDA-MB-435 and their non-metastatic 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.
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