Characteristics of miRNA-SNPs in healthy Japanese subjects and non-small cell lung cancer, colorectal cancer, and soft tissue sarcoma patients.

日本健康受试者和非小细胞肺癌的 miRNA - SNPs 特征,结直肠癌,软组织肉瘤患者.

• 发表时间: Sep 2021
• 来源期刊: Noncoding RNA Res
• DOI: 10.1016/j.ncrna.2021.06.002
• PMID: 34322648
• 文章类型: Journal Article
• 作者列表: Katayama K,Nakashima S,Ishida H,Kubota Y,Nakano M,Fukami T,Sasaki Y,Fujita KI,Nakajima M

关键词: 3′-UTR, 3′-untranslated region; BWA, Burrows-Wheeler Aligner; Biomarker; CI, confidence interval; CRC, colorectal cancer; GATK, Genome Analysis Toolkit; InDel, insertion or deletion mutation; NGS; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; Polymorphisms; SNP, single nucleotide polymorphism; STS, soft tissue sarcoma; mOR, modified odds ratio; miRNA, microRNA; microRNA; pre-miRNA, precursor miRNA

Abstract

Single nucleotide polymorphisms in genes encoding microRNAs (miRNA-SNPs) may affect the maturation steps of miRNAs or target mRNA recognition, leading to changes in the expression of target mRNAs to cause gain- or loss-of-function changes. Several miRNA-SNPs are known to be associated with the risk of diseases such as cancer. The purpose of this study was to comprehensively determine the miRNA-SNPs in Japanese individuals to evaluate the differences in allele frequencies between ethnicities by comparing data from the global population in the 1000 Genomes Project and differences between healthy subjects and cancer patients. We performed next-generation sequencing targeting genes encoding 1809 pre-miRNAs. As a result, 403 miRNA-SNPs (146 miRNA-SNPs per subject on average) were identified in 28 healthy Japanese subjects. We observed significant differences in the allele frequencies between ethnicities in 33 of the 403 miRNA-SNPs. The numbers of miRNA-SNPs per subject in 44 non-small cell lung cancer (NSCLC), 33 colorectal cancer (CRC), and 15 soft tissue sarcoma (STS) patients were almost equal to those in healthy subjects. Significant differences in allele frequencies were observed for 14, 11, and 9 miRNA-SNPs in NSCLC, CRC, and STS patients compared with the frequencies in healthy subjects, suggesting that these SNPs can be biomarkers of risk for each type of cancer assessed. In summary, we comprehensively characterized miRNA-SNPs in Japanese individuals and found differences in allele frequencies of several miRNA-SNPs between ethnicities and between healthy subjects and cancer patients. Studies investigating a larger number of subjects should be performed to confirm the potential of miRNA-SNPs as biomarkers of cancer risk.

摘要

编码microRNAs(miRNA-SNPs)的基因中的单核苷酸多态性可能影响miRNA的成熟步骤或靶mRNA识别,导致目标mRNA表达的变化，从而引起功能增加或丧失的变化。已知几种miRNA-SNP与疾病如癌症的风险相关。这项研究的目的是通过比较1000基因组计划中全球人群的数据以及健康受试者和癌症患者之间的差异，全面确定日本个体中的miRNA-SNP，以评估种族之间等位基因频率的差异。我们进行了下一代测序靶向编码1809pre-miRNA的基因。因此,在28名健康的日本受试者中鉴定了403个miRNA-SNP(每个受试者平均146个miRNA-SNP)。我们观察到403个miRNA-SNP中的33个种族之间的等位基因频率存在显着差异。44例非小细胞肺癌（NSCLC）中每位受试者的miRNA-SNP数量，33结直肠癌（CRC），15例软组织肉瘤（STS）患者几乎与健康受试者相同。在NSCLC中观察到14、11和9个miRNA-SNP的等位基因频率存在显着差异。CRC,和STS患者与健康受试者的频率相比，提示这些SNPs可能是评估每种癌症风险的生物标志物。总之,我们对日本个体的miRNA-SNP进行了全面的表征,并发现了不同种族之间以及健康受试者和癌症患者之间几种miRNA-SNP的等位基因频率存在差异.应进行调查大量受试者的研究，以确认miRNA-SNP作为癌症风险生物标志物的潜力。