SNP rs12982687 影响 lncRNA UCA1 与 miR-873-5p 的结合能力：参与吸烟引发的结直肠癌进展。

SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression.

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China.

Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

出版信息

Cell Commun Signal. 2020 Mar 6;18(1):37. doi: 10.1186/s12964-020-0518-0.

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.

背景

本研究旨在探讨长链非编码 RNA UCA1 的单核苷酸多态性（SNP）是否通过与环境暴露相互作用而增加结直肠癌（CRC）的风险。

方法

首先采用 lncRNA SNP 数据库预测可能影响 UCA1 与 miRNA 结合的 SNPs，然后通过 2 型基因-环境相互作用（GEI）模型评估 SNPs 与环境暴露对 CRC 风险的交互作用。此外，还进行了 MTT 测定、集落形成测定、transwell 测定和划痕愈合测定，以评估携带特定 SNP 不同基因型的 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 （尤其是 miR-873-5p）的结合能力。mirPath 软件预测的受 UCA1 调节的 miRNA 共享了富集在 HIF1 信号通路中的基因。此外，rs12982687 的纯合 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。相反，降低 UCA1 表达的 miR-873-5p 模拟物延迟了 CRC 细胞的转移（均 P<0.05）。此外，尼古丁不仅增加了 CRC 细胞中 UCA1 和 HIF-1α 的表达，还促进了 CRC 细胞的增殖和转移（P<0.05）。