2nd Department of Medicine, Faculty of Medicine, Semmelweis University, H-1088 Budapest, Szentkirályi str. 46, Hungary.
J Endocrinol Invest. 2013 Dec;36(11):1011-9. doi: 10.3275/9024. Epub 2013 Jul 1.
MicroRNA are involved in the pathogenesis of several tumors, and several studies have been performed on the microRNA profile of adrenocortical tumors to date. The pathways affected by these microRNA, however, have not been analyzed yet by a systematic approach.
To perform an in silico bioinformatics analysis of microRNA commonly altered in at least two studies and to decipher the pathways affected by microRNA in adrenocortical tumors.
Datasets on microRNA and mRNA expression have been retrieved from 5 and 3 studies, respectively. MicroRNA mRNA targets have been identified by our tissue specific target prediction pipeline, and mRNA have been subjected to Ingenuity Pathway Analysis.
Thirty- nine microRNA were identified as commonly altered in two studies. Altogether 49,817 mRNA targets have been found for these microRNA. One-hundred and seventy-eight significant pathways associating with these have been identified and were found in all studies. We have selected 12 pathways involving retinoic acid signaling (lipopolysaccharide/ interleukin-1 mediated inhibition of retinoic X receptor (RXR) function, peroxisome proliferator-activated receptor (PPAR)α/RXRα activation, retinoic A receptor activation and PPAR signaling pathways) and cell cycle alterations (aryl hydrocarbon receptor signaling, growth arrest and DNA damage-inducible 45 signaling, integrin signaling, G2/M DNA damage checkpoint regulation, cyclins and cell cycle regulation and cell cycle control of chromosomal replication pathways) as these have been also established in our previous study on the functional genomics meta-analysis of adrenocortical tumors. Several microRNA have been identified that could affect these pathways.
MicroRNA might affect several pathogenic pathways in adrenocortical tumors. Validation studies are required to confirm the biological relevance of these findings.
MicroRNA 参与了多种肿瘤的发病机制，目前已有多项研究针对肾上腺皮质肿瘤的 microRNA 谱进行了研究。然而，这些 microRNA 影响的途径尚未通过系统的方法进行分析。
对至少两项研究中常见改变的 microRNA 进行计算机生物信息学分析，并阐明 microRNA 对肾上腺皮质肿瘤的影响途径。
从 5 项和 3 项研究中分别检索 microRNA 和 mRNA 表达数据集。通过我们的组织特异性靶标预测管道识别 microRNA 的 mRNA 靶标，并对 mRNA 进行 Ingenuity 通路分析。
确定了 39 个在两项研究中常见改变的 microRNA。这些 microRNA 总共找到了 49817 个 mRNA 靶标。已经鉴定出与这些靶标相关的 178 个显著途径，并在所有研究中都有发现。我们选择了 12 个涉及视黄酸信号（脂多糖/白细胞介素-1 介导的视黄酸受体（RXR）功能抑制、过氧化物酶体增殖物激活受体（PPAR）α/RXRα激活、视黄酸受体激活和 PPAR 信号通路）和细胞周期改变（芳烃受体信号、生长停滞和 DNA 损伤诱导 45 信号、整合素信号、G2/M DNA 损伤检查点调节、细胞周期蛋白和细胞周期调控以及染色体复制途径的细胞周期调控）的途径，因为这些途径在我们之前对肾上腺皮质肿瘤功能基因组学荟萃分析的研究中也已确立。已经确定了一些可以影响这些途径的 microRNA。
MicroRNA 可能影响肾上腺皮质肿瘤中的多种致病途径。需要验证研究来确认这些发现的生物学相关性。
