Liu Junbiao, Li Yan
Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Biochem Biophys Res Commun. 2015 Nov 13;467(2):242-7. doi: 10.1016/j.bbrc.2015.09.182. Epub 2015 Oct 5.
MicroRNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Increasing evidence suggests that miRNAs are functionally important in cancers. We demonstrated miR-204 exerts its function by targeting gene involved in tumor growth and chemotherapy drugs reactivity. Here, we show that Trichostatin A (TSA) could increase ERα expression in MCF-7 and MDA-MB-231 cells by reducing miR204. Analysis of tumors growth inhibition shows that TSA promotes ERα expression, which could be reversed by miR-204 mimic transfection. When miR-204 is down regulated, the inhibition of TAM on breast cancer cells is enhanced. Caspase 3 activity is also increased. TSA and TAM combination inhibits Mcl-1 expression by decreasing phosphorylation of AKT induced by ERα increase in vivo and in vitro.
微小RNA(miR)是在人类肿瘤中异常表达的小非编码RNA。越来越多的证据表明,miRNA在癌症中具有重要功能。我们证明了miR-204通过靶向参与肿瘤生长和化疗药物反应性的基因发挥其功能。在这里,我们表明曲古抑菌素A(TSA)可以通过降低miR204来增加MCF-7和MDA-MB-231细胞中雌激素受体α(ERα)的表达。肿瘤生长抑制分析表明,TSA促进ERα表达,而miR-204模拟物转染可逆转这种促进作用。当miR-204下调时,他莫昔芬(TAM)对乳腺癌细胞的抑制作用增强。半胱天冬酶3(Caspase 3)活性也增加。TSA和TAM联合使用在体内和体外通过降低ERα增加诱导的AKT磷酸化来抑制髓细胞白血病-1(Mcl-1)表达。