Clinical significance of miR-144-ZFX axis in disseminated tumour cells in bone marrow in gastric cancer cases.
Clinical significance of miR-144-ZFX axis in disseminated tumour cells in bone marrow in gastric cancer cases.
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DOI：
10.1038/bjc.2012.326
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发表时间：
2012-10-09
影响因子：
8.8
通讯作者：
Mori, M.
中科院分区：
文献类型：
--
作者：
Akiyoshi, S.;Fukagawa, T.;Ueo, H.;Ishibashi, M.;Takahashi, Y.;Fabbri, M.;Sasako, M.;Maehara, Y.;Mimori, K.;Mori, M.
我们以前曾报道骨髓（BM）是胃癌（GC）细胞的归巢部位，导致血行转移。关于microRNA在BM中调控恶性细胞或宿主细胞中的通路，从而调控GC进展的研究很少。对来自BM的总RNA进行了microRNA微阵列和基因表达微阵列分析，比较了5名早期和5名晚期GC患者。我们专注于miR-144-ZFX轴作为GC进展的候选BM调节因子，并通过磁激活细胞分选（MACS）验证了不同细胞组分（EpCAM+ CD 45 −，EpCAM− CD 45+和CD 14+）中microRNA表达的起源。定量逆转录酶（RT）-PCR分析证实，与I期GC患者相比，IV期GC患者中miR-144表达减少（t检验，P=0.02），与ZFX呈负相关（ANOVA，P<0.01）。在5个GC细胞系中的荧光素酶报告基因测定表明它们直接结合，并通过蛋白质印迹法进行验证。pre-miR 144处理和由此产生的GC细胞系中ZFX的抑制适度上调了它们对5-氟尿嘧啶化疗的敏感性。在MACS纯化的BM组分中，miR-144表达水平在播散性肿瘤细胞组分中显著降低（P=0.0005）。在93例原发性胃癌中，miR-144表达降低，提示预后不良。我们推测，当miR-144的低表达允许ZFX的上调时，播散性癌细胞可以在BM中存活。癌细胞中miR-144-ZFX轴的调节在GC病例进展的指标中具有关键作用。
We previously reported that bone marrow (BM) was a homing site for gastric cancer (GC) cells leading to haematogenous metastases. There has been little study that microRNAs regulated pathways in malignant cells or host cells in BM, and thereby regulated the progression of GC. Both microRNA microarray and gene expression microarray analyses of total RNA from BM were conducted, comparing five early and five advanced GC patients. We focused on miR-144-ZFX axis as a candidate BM regulator of GC progression and validated the origin of the microRNA expression in diverse cell fractions (EpCAM+CD45−, EpCAM−CD45+, and CD14+) by magnetic-activated cell sorting (MACS). Quantitative reverse-transcriptase (RT)–PCR analysis validated diminished miR-144 expression in stage IV GC patients with respect to stage I GC patients (t-test, P=0.02), with an inverse correlation to ZFX (ANOVA, P<0.01). Luciferase reporter assays in five GC cell lines indicated their direct binding and validated by western blotting. Pre-miR144 treatment and the resultant repression of ZFX in GC cell lines moderately upregulated their susceptibility to 5-fluorouracil chemotherapy. In MACS-purified BM fractions, the level of miR-144 expression was significantly diminished in disseminated tumour cell fraction (P=0.0005). Diminished miR-144 expression in 93 cases of primary GC indicated poor prognosis. We speculate that disseminated cancer cells could survive in BM when low expression of miR-144 permits upregulation of ZFX. The regulation of the miR-144-ZFX axis in cancer cells has a key role in the indicator of the progression of GC cases.
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影响因子：
4.4
作者：
Iwahashi H;Kitagawa E;Suzuki Y;Ueda Y;Ishizawa YH;Nobumasa H;Kuboki Y;Hosoda H;Iwahashi Y
通讯作者：
Iwahashi Y
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
影响因子：
20.3
作者：
Garzon, Ramiro;Volinia, Stefano;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
DOI：
10.1073/pnas.0404432101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Calin, GA;Liu, CG;Croce, CM
通讯作者：
Croce, CM
DOI：
10.1016/j.urolonc.2007.01.019
发表时间：
2007-09-01
影响因子：
2.7
作者：
Gottardo, Fedra;Liu, Chang Gong;Baffa, Raffaele
通讯作者：
Baffa, Raffaele