Hershkovitz-Rokah Oshrat, Geva Polina, Salmon-Divon Mali, Shpilberg Ofer, Liberman-Aronov Stella
Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, Israel.
Translational Research Laboratory, Assuta Medical Centers, Tel Aviv, Israel.
Oncotarget. 2018 Jan 5;9(8):7928-7941. doi: 10.18632/oncotarget.23974. eCollection 2018 Jan 30.
MicroRNAs (miRs) are short non-coding regulatory RNAs that control gene expression at the post-transcriptional level and play an important role in cancer development and progression, acting either as oncogenes or as tumor suppressors. Identification of aberrantly expressed miRs in patients with hematological malignancies as compared to healthy individuals has suggested that these molecules may serve as novel clinical diagnostic and prognostic biomarkers. We conducted a systematic literature review of articles published between 2007 and 2017 and re-analyzed experimentally-validated human miR expression signatures in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from various biological sources (tumor tissue, peripheral blood, bone marrow and cell lines). A unique miR expression pattern was observed for each disease. Compared to healthy individuals, 61 miRs were aberrantly expressed in DLBCL and 85 in FL; 20-30% of aberrantly expressed miRs overlapped between the two lymphoma subtypes. Analysis of integrative positive and negative miRNA-mRNA relationships using the Ingenuity Pathway Analysis (IPA) system revealed 970 miR-mRNA pairs for DLBCL and 90 for FL. Through gene ontology analysis, we found potential regulatory pathways that are deregulated in DLBCL and FL due to improper expression of miR target genes. By comparing the expression level of the aberrantly expressed miRs in DLBCL to their expression levels in other malignancies, we identified seven miRs that are aberrantly expressed in DLBCL tumor tissues (miR-15a, miR-16, miR-17, miR-106, miR-21, miR-155 and miR-34a-5p). This specific expression pattern may be a potential diagnostic tool for DLBCL.
微小RNA（miR）是短链非编码调节性RNA，可在转录后水平控制基因表达，在癌症发生和发展过程中发挥重要作用，其作用方式既可以是癌基因，也可以是肿瘤抑制因子。与健康个体相比，血液系统恶性肿瘤患者中异常表达的miR的鉴定表明，这些分子可能作为新型临床诊断和预后生物标志物。我们对2007年至2017年间发表的文章进行了系统的文献综述，并重新分析了来自各种生物学来源（肿瘤组织、外周血、骨髓和细胞系）的弥漫性大B细胞淋巴瘤（DLBCL）和滤泡性淋巴瘤（FL）中经过实验验证的人类miR表达特征。每种疾病都观察到独特的miR表达模式。与健康个体相比，DLBCL中有61种miR异常表达，FL中有85种；两种淋巴瘤亚型之间20-30%的异常表达miR存在重叠。使用Ingenuity Pathway Analysis（IPA）系统分析整合的正向和负向miRNA-mRNA关系，发现DLBCL有970对miR-mRNA，FL有90对。通过基因本体分析，我们发现由于miR靶基因表达不当，DLBCL和FL中潜在的调控途径失调。通过比较DLBCL中异常表达的miR的表达水平与其在其他恶性肿瘤中的表达水平，我们鉴定出7种在DLBCL肿瘤组织中异常表达的miR（miR-15a、miR-16、miR-17、miR-106、miR-21、miR-155和miR-34a-5p）。这种特定的表达模式可能是DLBCL的一种潜在诊断工具。
