BACKGROUND This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. METHODS LncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised. RESULTS SNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P < 0.05). Additionally, nicotine not merely elevated UCA1 and HIF-1α expressions in CRC cells, but also facilitated proliferation and metastasis of CRC cells (P < 0.05). CONCLUSIONS SNP rs12982687 was involved in smoking-triggered CRC progression, given its influence on UCA1's binding with miR-873-5p and HIF-1 signaling.

中文翻译：

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SNP rs12982687影响lncRNA UCA1与miR-873-5p的结合能力：参与吸烟触发的结直肠癌的进展。

背景技术本研究旨在阐明lncRNA UCA1的单核苷酸多态性（SNP）是否与环境暴露相互作用而导致大肠癌（CRC）风险升高。方法首先采用LncRNASNP数据库预测可能影响UCA1与miRNA结合的SNP，然后通过重复2型基因-环境相互作用（GEI）模型评估SNP与环境暴露对CRC风险的相互作用。此外，进行MTT测定，集落形成测定，transwell测定和伤口愈合测定，以评估携带不同基因型的特定SNP的CRC细胞系的活性。还评估了尼古丁对CRC细胞活性的影响。结果UCA1的SNP rs12982687干预了UCA1与几种miRNA的结合能力，特别是miR-873-5p。如mirPath软件所预测，受UCA1调控的MiRNA共享的基因富含HIF1信号通路。此外，rs12982687的纯合子TT降低了吸烟者的CRC风险，携带rs12982687（CC）的CRC细胞表现出较强的迁移和侵袭能力。相比之下，减少UCA1表达的miR-873-5p模拟物可延迟CRC细胞的转移（所有P <0.05）。此外，尼古丁不仅提高了CRC细胞中UCA1和HIF-1α的表达，而且还促进了CRC细胞的增殖和转移（P <0.05）。结论SNP rs12982687参与了吸烟触发的CRC进展，因为它对UCA1与miR-873-5p和HIF-1信号传导的结合产生影响。此外，rs12982687的纯合子TT降低了吸烟者的CRC风险，携带rs12982687（CC）的CRC细胞表现出较强的迁移和侵袭能力。相比之下，减少UCA1表达的miR-873-5p模拟物可延迟CRC细胞的转移（所有P <0.05）。此外，尼古丁不仅提高了CRC细胞中UCA1和HIF-1α的表达，而且还促进了CRC细胞的增殖和转移（P <0.05）。结论SNP rs12982687参与了吸烟触发的CRC进展，因为它对UCA1与miR-873-5p和HIF-1信号传导的结合产生影响。此外，rs12982687的纯合子TT降低了吸烟者的CRC风险，携带rs12982687（CC）的CRC细胞表现出较强的迁移和侵袭能力。相比之下，减少UCA1表达的miR-873-5p模拟物可延迟CRC细胞的转移（所有P <0.05）。此外，尼古丁不仅提高了CRC细胞中UCA1和HIF-1α的表达，而且还促进了CRC细胞的增殖和转移（P <0.05）。结论SNP rs12982687参与了吸烟触发的CRC进展，因为它对UCA1与miR-873-5p和HIF-1信号传导的结合产生影响。此外，尼古丁不仅提高了CRC细胞中UCA1和HIF-1α的表达，而且还促进了CRC细胞的增殖和转移（P <0.05）。结论SNP rs12982687参与了吸烟触发的CRC进展，因为它对UCA1与miR-873-5p和HIF-1信号传导的结合产生影响。此外，尼古丁不仅提高了CRC细胞中UCA1和HIF-1α的表达，而且还促进了CRC细胞的增殖和转移（P <0.05）。结论SNP rs12982687参与了吸烟触发的CRC进展，因为它对UCA1与miR-873-5p和HIF-1信号传导的结合产生影响。