A functional variant rs353292 in the flanking region of miR-143/145 contributes to the risk of colorectal cancer.
A functional variant rs353292 in the flanking region of miR-143/145 contributes to the risk of colorectal cancer.
复制标题
miR-143/145 侧翼区域的功能性变异 rs353292 会增加结直肠癌的风险
DOI：
10.1038/srep30195
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发表时间：
2016-07-22
影响因子：
4.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Yuan F;Sun R;Li L;Jin B;Wang Y;Liang Y;Che G;Gao L;Zhang L
MicroRNA（miR）-143和miR-145已被确定为细胞增殖、细胞生长、克隆形成、细胞凋亡、细胞周期、侵袭和迁移的分子调节因子。我们先前发现miR-143/145侧翼区的rs353292在结直肠癌（CRC）患者中显示出高频率。为了确定rs353292多态性是否是结直肠癌的危险因素，我们用更大的样本进行了这项研究。共收集了809例CRC患者和1005例性别匹配的对照。采用TaqMan等位基因判别法对rs353292多态性进行基因分型。采用双荧光素酶报告基因分析法检测其转录活性。我们发现rs353292多态性与杂合子比较中发生CRC的风险增加相关，（校正OR = 1.70，95%CI，1.32- 2.20，P < 0.001），显性遗传模型（校正OR = 1.62，95%CI，1.26- 2.09，P < 0.001），等位基因比较（校正OR = 1.46，95%CI，1.16- 1.84，P = 0.001）。与CC携带者相比，rs353292 CT/TT携带者表现出较低的miR-143表达（P= 0.04）。pGL 3-rs353292 T的荧光素酶活性显著低于pGL 3-rs353292 C（P< 0.01）。这些发现表明，rs353292多态性是功能性的，可能是CRC发生的危险因素。
MicroRNA (miR)-143 and miR-145 have been identified as molecular regulators in cell proliferation, cell growth, clone formation, apoptosis, cell cycle, invasion, and migration. We previously found that rs353292 in the flanking region of miR-143/145 showed a high frequency in patients with colorectal cancer (CRC). To identify whether the rs353292 polymorphism is a risk factor for CRC, we conducted this study with larger samples. A total of 809 patients with CRC and 1005 gender matched controls were collected. The rs353292 polymorphism was genotyped by using TaqMan allelic discrimination. Dual luciferase reporter assay was carried out to measure the transcriptional activity. We found that the rs353292 polymorphism was associated with an increased risk for developing CRC in heterozygous comparison (adjusted OR = 1.70, 95% CI, 1.32–2.20,P< 0.001), dominant genetic model (adjusted OR = 1.62, 95% CI, 1.26–2.09,P< 0.001), and allele comparison (adjusted OR = 1.46, 95% CI, 1.16–1.84,P= 0.001). The rs353292 CT/TT carriers exhibited a lower expression of miR-143 compared to the CC carriers (P= 0.04). Moreover, the pGL3-rs353292T displayed a significantly lower luciferase activity than pGL3-rs353292C (P< 0.01). These findings indicate that the rs353292 polymorphism is functional and may be a risk factor for the development of CRC.