A SNP-mediated lncRNA (LOC146880) and microRNA (miR-539-5p) interaction and its potential impact on the NSCLC risk
A SNP-mediated lncRNA (LOC146880) and microRNA (miR-539-5p) interaction and its potential impact on the NSCLC risk
复制标题
DOI：
10.1186/s13046-020-01652-5
复制
发表时间：
2020-08-14
影响因子：
11.3
通讯作者：
Qian, Biyun
中科院分区：
文献类型：
--
作者：
Feng, Tienan;Feng, Nannan;Qian, Biyun
许多与癌症相关的单核苷酸多态性（SNP）位于长链非编码RNA（lncRNA）的基因组区域。这些SNPs与癌症风险相关的机制尚未完全了解。方法采用病例对照研究方法，对2707例非小细胞肺癌（NSCLC）患者的lncRNALOC 146880位点rs 140618127单核苷酸多态性进行分析。通过体外和体内实验探索SNP的生物学影响的机制，包括质粒转染、siRNA敲低、流式细胞术评估以及细胞增殖、迁移、侵袭和集落形成的测定。结果SNP rs 140618127的A等位基因与中国人群NSCLC的低风险相关。实验室实验表明，SNP rs 140618127含有miR-539- 5 p的结合位点，并且miR-539- 5 p和LOC 146880之间的结合导致癌基因ENO 1的磷酸化下降。ENO 1磷酸化的减少导致PI 3 K和Akt磷酸化的减少，这进一步与细胞增殖和肿瘤进展的下降有关。结论lncRNA loc 146880中的SNP rs 140618127为microRNA miR-539- 5 p提供了替代结合位点，影响ENO 1的磷酸化及PI 3 K和Akt通路的激活。
Background Many cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood. Methods Association of SNP (rs140618127) in lncRNALOC146880with non-small cell lung cancer (NSCLC) was evaluated in a case-control study of 2707 individuals. The mechanism of the SNP's biologic influence was explored with in vitro and in vivo experiments, including plasmid transfection, siRNA knockdown, flow cytometry assessment, and assays of cell proliferation, migration, invasion, and colony formation. Results Association analysis showed that A allele of SNP rs140618127 was associated with low risk of NSCLC in the Chinese population. Lab experiments indicated that SNP rs140618127 contained a binding site for miR-539-5p and the binding between miR-539-5p andLOC146880resulted in declined phosphorylation of an oncogene, ENO1. The reduced phosphorylation of ENO1 led to decreased phosphorylation of PI3K and Akt, which is further linked to the decline in cell proliferation and tumor progression. Conclusion The study demonstrates that SNP rs140618127 in lncRNA loc146880 provides an alternate binding site for microRNA miR-539-5p which affects the phosphorylation of ENO1 and activation of the PI3K and Akt pathway.