NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer.
NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer.
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启动子甲基化介导的NGX6基因作为结直肠癌的潜在分子标记
DOI：
10.1186/1471-2407-10-160
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发表时间：
2010-04-27
期刊：
影响因子：
3.8
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Liu M;Peng Y;Wang X;Guo Q;Shen S;Li G
背景：在大多数结肠癌细胞系和肿瘤组织中，鼻咽癌相关基因6 （NGX6）与正常组织样本相比表达下调。它是一种新的抑制肿瘤的基因，可以抑制结肠癌细胞的生长和细胞周期的进展。然而，调控NGX6基因表达的转录机制尚不清楚。最近的研究结果表明，多种肿瘤抑制基因的表观遗传失活在结直肠癌（CRC）的肿瘤发生中起重要作用。在这项研究中，我们探讨了DNA甲基化在NGX6转录调控中的作用。方法利用荧光素酶报告基因法克隆具有CpG岛特征的NGX6启动子。然后，利用甲基化特异性PCR和亚硫酸氢盐DNA测序检测结肠癌细胞系和结直肠肿瘤组织中NGX6启动子区周围CpG甲基化状态。最后，利用5-Aza-2'-脱氧胞苷（5-Aza-dC）处理证实NGX6启动子甲基化与其基因失活之间的相关性。结果鉴定出-157 ~ +276位序列为NGX6启动子，未发现典型的TATA盒，但发现两个CAAT盒和GC盒。40例结直肠癌标本的甲基化状态高于40例相邻正常粘膜标本（18/40比7/40，P < 0.05）。一项将基因甲基化状态与临床病理癌症特征相关联的分析显示，NGX6启动子的密集甲基化与结直肠癌患者的年龄相关（P < 0.05）。此外，NGX6启动子甲基化与结直肠癌的转移状态和原发部位相关（p = 0.056和p = 0.067）。此外，5-Aza-dC可诱导HT-29细胞中NGX6 mRNA的表达和NGX6启动子的去甲基化。结论NGX6基因下调与启动子甲基化有关。NGX6启动子的DNA甲基化可能是诊断或预后的潜在分子标记，或作为治疗靶点。
BackgroundNasopharyngeal carcinoma associated gene 6 (NGX6) is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC). In this study, we explored the role of DNA methylation in regulation of NGX6 transcription.MethodsIn the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation.ResultsThe sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P < 0.05). An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the NGX6 promoter was associated with colorectal cancer patients age (P < 0.05). Moreover, a trend was shown toward metastasis status and primary site in colorectal carcinomas with NGX6 promoter methylation (p = 0.056 and P = 0.067, respectively). In addition, 5-Aza-dC could induce NGX6 mRNA expression and NGX6 promoter demethylation in HT-29 cells.ConclusionsDown-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target.
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DOI：
10.1158/1078-0432.ccr-08-1029
发表时间：
2009-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kumar K;Brim H;Giardiello F;Smoot DT;Nouraie M;Lee EL;Ashktorab H
通讯作者：
Ashktorab H
影响因子：
11.2
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Yi JM;Tsai HC;Glöckner SC;Lin S;Ohm JE;Easwaran H;James CD;Costello JF;Riggins G;Eberhart CG;Laterra J;Vescovi AL;Ahuja N;Herman JG;Schuebel KE;Baylin SB
通讯作者：
Baylin SB
影响因子：
6.2
作者：
Vilkin, Alex;Niv, Yaron;Nagasaka, Takeshi;Morgenstern, Sarah;Levi, Zohar;Fireman, Zvi;Fuerst, Florentine;Goel, Ajay;Boland, C. Richard
通讯作者：
Boland, C. Richard
影响因子：
4.5
作者：
Kim HC;Lee HJ;Roh SA;Kim JS;Yu CS;Kim JC
通讯作者：
Kim JC
影响因子：
5.6
作者：
GARDINERGARDEN, M;FROMMER, M
通讯作者：
FROMMER, M