Jumonji Domain Containing 1A Is a Novel Prognostic Marker for Colorectal Cancer: In vivo Identification from Hypoxic Tumor Cells
Jumonji Domain Containing 1A Is a Novel Prognostic Marker for Colorectal Cancer: In vivo Identification from Hypoxic Tumor Cells
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DOI：
10.1158/1078-0432.ccr-10-0407
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发表时间：
2010-09-15
影响因子：
11.5
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Uemura, Mamoru;Yamamoto, Hirofumi;Mori, Masaki
目的：本研究旨在确定新的缺氧诱导和预后标志物在体内从缺氧肿瘤cells.Experimental Design：使用碳酸酐酶9和CD 34作为一个指导缺氧肿瘤细胞，激光捕获显微切割被用来分离结直肠癌（CRC）肝转移。通过微阵列分析来分析样品，与在缺氧条件下培养的五种CRC细胞系平行。为了评估某些基因表达的预后影响，通过微阵列或定量逆转录PCR分析了来自总共356名CRC患者的样本。对组蛋白H3 Lys（9）去甲基化酶Jumonji domain containing 1A（JMJD 1A）进行了体外机制研究和体内治疗实验。其中，我们发现JMJD 1A是一个新的独立的预后因素（P = 0.013）。体外试验显示，小干扰RNA处理导致的JMJD 1A的丢失与CRC细胞系增殖活性的降低和侵袭性的降低相关。结论：JMJD 1A是一种有效的肿瘤细胞缺氧标志物，可作为肿瘤细胞的预后标志物，有望成为大肠癌治疗的新靶点。临床癌症研究; 16（18）; 4636-46。(c)2010年AACR。
Purpose: This study aimed to identify novel hypoxia-inducible and prognostic markers in vivo from hypoxic tumor cells.Experimental Design: Using carbonic anhydrase 9 and CD34 as a guide for hypoxic tumor cells, laser capture microdissection was used to isolate colorectal cancer (CRC) liver metastases. The samples were analyzed by microarray analysis, in parallel with five CRC cell lines cultured under hypoxic conditions. To evaluate the prognostic impact of the expression of certain genes, samples from a total of 356 CRC patients were analyzed by microarray or quantitative reverse transcription-PCR. In vitro mechanistic studies and in vivo therapeutic experiments were also done about a histone H3 Lys(9) demethylase, Jumonji domain containing 1A (JMJD1A).Results: Several candidate genes were identified by microarray analysis of liver metastases and culturing of CRC cells under hypoxic conditions. Among them, we found that JMJD1A was a novel independent prognostic factor for CRC (P = 0.013). In vitro assays revealed that loss of JMJD1A by small interfering RNA treatment was associated with a reduction of proliferative activity and decrease in invasion of CRC cell lines. Furthermore, treatment with an adenovirus system for antisense JMJD1A construct displayed prominent therapeutic effects when injected into established tumor xenografts of the CRC cell lines HCT116 and DLD1.Conclusions: JMJD1A is a useful biomarker for hypoxic tumor cells and a prognostic marker that could be a promising therapeutic target against CRC. Clin Cancer Res; 16(18); 4636-46. (c) 2010 AACR.