A polymorphism in miR‐1262 regulatory region confers the risk of lung cancer in Chinese population

Abstract

It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis.

CeRNA Network Analysis Representing Characteristics of Different Tumor Environments Based on 1p/19q Codeletion in Oligodendrogliomas

“…In addition, in the results of an expanded study on lower grade glioma, more statistically significant genes were found. There were reports with findings consistent with those of ours on hsa-miR-1262, hsa-miR-455-3p, LPAL2 [83][84][85][86], and some reports even contradicted our findings on hsa-miR-204-5p and hsa-miR-197-3p [87,88]. Although related studies are still insufficient, the previous report about hsa-miR-186-5p in glioblastoma contradicted our findings [89].…”

The association between polymorphisms in microRNA genes and cervical cancer in a Chinese Han population

“…Evidence has shown that miRNAs are involved in the initiation and development of various types of cancers, and these molecules function as anti-oncogenes or oncogenes. SNPs in miRNAs, including primary, precursor and mature miRNA, may change the expression level and alter the binding affinity of miRNAs, and further regulate the expression of the target genes, thereby markedly impacting cell pathway regulation, which defines cellular fates [ 19 , 20 ]. In the present study, we observed that rs11134527 in pri-miR-218-2 and rs531564 in pri-miR-124-1 were associated with CIN and cervical cancer in a Chinese Han population.…”

Polymorphisms of rs1347093 and rs1397529 are associated with lung cancer risk in northeast Chinese population

“…In recent years, more and more studies about the association between SNPs and lung cancer risk were conducted. The studies of Chen D [ 18 ], Xie K [ 19 ], Yin Z [ 20 ] et al all came to a significant conclusion. SNPs play an important role in the occurrence, development and prognosis of lung cancer [ 21 ].…”