Yang C, Sun C, Liang X, Xie S, Huang J, Li D
Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, China.
Department of Thoracic Surgery, People's Hospital of Wuhan University, Wuhan, China.
Cancer Gene Ther. 2016 Apr;23(4):90-7. doi: 10.1038/cgt.2016.5. Epub 2016 Mar 11.
Non-small-cell lung cancer (NSCLC) represents the most common deadly disease. Emerging evidences suggest that abnormal epigenetic modulation via mRNAs and microRNAs (miRNAs) might be involved in the tumorigenesis. To explore novel therapeutic target of NSCLC, a more detailed mRNAs and miRNA expression profiling study is needed. High-quality total RNA including miRNA was isolated from NSCLC tissue and para-carcinoma tissue and used for RNA and small RNA sequencing. Results were analyzed bioinformatically and validated using quantitative real-time (qRT)-PCR. A total of 3530 genes (1977 up-regulated and 1553 down-regulated) and 211 miRNAs (171 up-regulated and 30 down-regulated) were differentially expressed (DE) in NSCLC tissue versus adjacent normal tissues. Furthermore, 157 novel miRNAs were predicted in our samples. Of these, 918 significant miRNA-mRNA pairs were identified, consisting of 100 miRNAs and 443 mRNAs. Gene ontology analysis revealed that most of the target genes were enriched in the terms of plasma membrane, binding, and multiple biological-molecular signaling processes. Pathway analysis of these miRNA signatures highlights their critical roles in calcium signaling pathway. Using qRT-PCR, the expression of several DE genes (KRAS and RBM5) and miRNAs (miR-1-5p, let-7b-5p, miR-21-5p, miR-1290, miR-149-5p, chr8_28846, chrX_31594, and chr9_29897) were confirmed. The integrative analysis based on mRNA and miRNA profiling may provide more potential molecular for the tumorigenesis and development of NSCLC.
非小细胞肺癌（NSCLC）是最常见的致命疾病。新出现的证据表明，通过信使核糖核酸（mRNAs）和微小核糖核酸（miRNAs）进行的异常表观遗传调控可能参与肿瘤发生过程。为了探索NSCLC的新型治疗靶点，需要进行更详细的mRNAs和miRNA表达谱研究。从NSCLC组织和癌旁组织中分离出包括miRNA在内的高质量总RNA，并用于RNA和小RNA测序。对结果进行生物信息学分析，并使用定量实时（qRT）-PCR进行验证。与相邻正常组织相比，NSCLC组织中共有3530个基因（1977个上调和1553个下调）和211个miRNAs（171个上调和30个下调）差异表达（DE）。此外，在我们的样本中预测到157个新的miRNAs。其中，鉴定出918对显著的miRNA-mRNA对，由100个miRNAs和443个mRNAs组成。基因本体分析显示，大多数靶基因在质膜、结合和多种生物分子信号传导过程方面富集。对这些miRNA特征的通路分析突出了它们在钙信号通路中的关键作用。使用qRT-PCR，证实了几个DE基因（KRAS和RBM5）和miRNAs（miR-1-5p、let-7b-5p、miR-21-5p、miR-1290、miR-149-5p、chr8_28846、chrX_31594和chr9_29897）的表达。基于mRNA和miRNA谱的综合分析可能为NSCLC的肿瘤发生和发展提供更多潜在分子。
