Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC
Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC
复制标题
CCSlnc362 (RP11-362K14.5) 处的 SNP rs1317082 变体创建 miR-4658 的结合位点并降低对 CRC 的易感性
DOI：
10.1038/s41419-018-1222-5
复制
发表时间：
2018-12-05
影响因子：
9
通讯作者：
Hong, Jie
中科院分区：
文献类型：
--
作者：
Shen, Chaoqin;Yan, Tingting;Hong, Jie
全基因组关联研究（GWAS）已经确定了几个位点的变异影响结直肠癌的风险;然而，生殖系变异影响结直肠癌（CRC）肿瘤发生的具体机制仍然没有揭示。我们发现位于lncRNA RP 11 -362K14.5（CCSlnc 362）外显子1的rs 1317082的TC变异体被预测为癌症的保护性位点。然而，CCSlnc 362的具体作用以及CCSlnc 362与rs 1317082变异在结直肠癌中的相互作用及其机制尚不清楚。本研究探讨了CCSlnc 362在结直肠癌细胞和组织中的表达和功能。我们发现lncRNA CCSlnc 362的表达在CRC样品中显著增加。后续的功能实验表明，下调CCSlnc 362抑制细胞增殖，阻滞细胞周期，并促进CRC细胞凋亡。CCSlnc 362外显子1的rs 1317082的TC变体产生了miR-4658的结合位点，从而降低CCSlnc 362的表达，从而降低CRC的易感性。我们的研究结果为rs 1317082变异在CRC中的保护作用和lncRNA CCSlnc 362的潜在致癌作用提供了支持证据。这些数据揭示了生殖系变异，miRNAs和lncRNAs之间的关系，并为CRC的靶向治疗开辟了新的途径。
Genome-wide association studies (GWAS) have identified several loci harboring variants that affected the risk of colorectal cancer; however, the specific mechanisms by which germline variation influenced the tumorigenesis of colorectal cancer (CRC) remains unrevealed. We found the TC variant of rs1317082, locating at the exon 1 of lncRNA RP11-362K14.5 (CCSlnc362), was predicted to be a protective locus for cancer. However, the specific role of CCSlnc362 and the interaction between CCSlnc362 and rs1317082 variation in colorectal cancer and its mechanisms remain unclear. Here we explored the expression and function of CCSlnc362 in CRC cells and tissues. We found lncRNA CCSlnc362 expression was significantly increased in CRC samples. Follow-up functional experiments elucidated that downregulation of CCSlnc362 inhibited cell proliferation, arrested cell cycle, and promoted apoptosis in CRC cells. The TC variant of rs1317082 at CCSlnc362 exon 1 created a binding site for miR-4658 to reduce the expression of CCSlnc362 and thus decreased the susceptibility to CRC. Our findings have provided supporting evidence for the protective role of rs1317082 variation and the potential oncogenic role of lncRNA CCSlnc362 in CRC. The data shed new light on the relationship between germline variation, miRNAs, and lncRNAs and opened a new avenue for targeted therapy in CRC.