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综合分析异常表达的 microRNA 谱揭示了人类肺腺癌进展的潜在生物标志物。

Comprehensive analysis of aberrantly expressed microRNA profiles reveals potential biomarkers of human lung adenocarcinoma progression.

机构信息

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

Department of Thoracic Surgery, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, P.R. China.

出版信息

Oncol Rep. 2017 Oct;38(4):2453-2463. doi: 10.3892/or.2017.5880. Epub 2017 Aug 4.

DOI:10.3892/or.2017.5880
PMID:28791371
Abstract

Lung adenocarcinoma (LUAD) is a complex disease that poses challenges for diagnosis and treatment. The aim of the present study is to investigate LUAD-specific key microRNAs (miRNAs) from large-scale samples in The Cancer Genome Atlas (TCGA) database. We used an integrative computational method to identify LUAD-specific key miRNAs related to TNM stage and lymphatic metastasis from the TCGA database. Twenty-five LUAD-specific key miRNAs (fold change >2, p<0.05) from the TCGA database were investigated, and 15 were found to be aberrantly expressed with respect to clinical features. Three miRNAs were correlated with overall survival (log-rank p<0.05). Then, 5 miRNAs were randomly selected for verification of expression in 53 LUAD patient tissues using qRT-PCR. Diagnostic value of these above 5 miRNAs was determined by areas under receiver operating characteristic curves (ROC). Finally, the LUAD-related miRNA miR-30a-3p was selected for verification of biologic function in A549 cells. The results of tests for cell proliferation, apoptosis, and target genes suggested that miR-30a-3p decreases cell proliferation and promotes apoptosis through targeting AKT3. Therefore, miR-30a-3p may be a promising biomarker for the early screening of high-risk populations and early diagnosis of LUAD. Our studies provide insights into identifying novel potential biomarkers for diagnosis and prognosis of LUAD.

摘要

肺腺癌 (LUAD) 是一种复杂的疾病,在诊断和治疗方面存在挑战。本研究旨在从癌症基因组图谱 (TCGA) 数据库中大规模样本中研究 LUAD 特异性关键 microRNAs (miRNAs)。我们使用整合计算方法从 TCGA 数据库中鉴定与 TNM 分期和淋巴转移相关的 LUAD 特异性关键 miRNA。研究了来自 TCGA 数据库的 25 个 LUAD 特异性关键 miRNA(fold change >2,p<0.05),其中 15 个 miRNA 的表达与临床特征有关。有 3 个 miRNA 与总生存期相关(log-rank p<0.05)。然后,使用 qRT-PCR 在 53 个 LUAD 患者组织中随机选择 5 个 miRNA 进行验证表达。通过接受者操作特征曲线 (ROC) 下的面积确定这些 miRNA 的诊断价值。最后,选择与 LUAD 相关的 miRNA miR-30a-3p 验证在 A549 细胞中的生物学功能。通过细胞增殖、凋亡和靶基因的测试,结果表明 miR-30a-3p 通过靶向 AKT3 降低细胞增殖并促进凋亡。因此,miR-30a-3p 可能是 LUAD 高危人群早期筛查和早期诊断的有前途的生物标志物。我们的研究为鉴定 LUAD 诊断和预后的新型潜在生物标志物提供了思路。

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