Contrasting Expression Patterns of Histone mRNA and microRNA 760 in Patients with Gastric Cancer
Contrasting Expression Patterns of Histone mRNA and microRNA 760 in Patients with Gastric Cancer
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DOI：
10.1158/1078-0432.ccr-12-3186
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发表时间：
2013-12-01
影响因子：
11.5
通讯作者：
Mimori, Koshi
中科院分区：
文献类型：
--
作者：
Iwaya, Takeshi;Fukagawa, Takeo;Mimori, Koshi
目的：近年来的研究表明，骨髓中的肿瘤细胞和非癌细胞共同参与了肿瘤的进展。实验设计：将来自8名胃癌患者（I期和IV期：各n = 4）的骨髓样品用于RNA-seq分析。通过实时定量PCR（qRT-PCR）分析胃癌患者175例骨髓、92例外周血和115例原发性肿瘤样本中HIST 1H 3D的表达，验证了结果。使用qRT-PCR在105个骨髓和96个原发性肿瘤样品中测定miR-760表达。进行荧光素酶报告基因测定以确认组蛋白mRNA是否是miR-760的直接靶标。miR-760的表达也在胃癌患者的非癌细胞中进行了评估。结果：胃癌患者骨髓样本的RNA-seq分析显示，IV期患者中多种组蛋白mRNA的表达更高。IV期患者的骨髓、外周血和原发性肿瘤中的HIST 1H 3D表达高于I期患者（分别为P = 0.0284、0.0243和0.0006）。相比之下，与I期患者相比，IV期患者的骨髓和原发性肿瘤中miR-760下调（分别为P = 0.0094和0.0018）。组蛋白mRNA和miR-760直接相互作用。结论：进展期胃癌患者骨髓和原发灶中组蛋白mRNA表达上调，而miR-760表达下调，提示组蛋白mRNA/miR-760轴在胃癌的发生发展中起重要作用。临床癌症研究; 19（23）; 6438-49。(C)2013年AACR。
Purpose: Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer.Experimental Design: Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients.Results: RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P = 0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNA and miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients.Conclusion: Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer. Clin Cancer Res; 19(23); 6438-49. (C) 2013 AACR.