microRNA expression in autonomous thyroid adenomas: correlation with mRNA regulation. Homo sapiens

MicroRNA (miRNA) are a class of small non-coding RNAs that act on the stability and the translation efficiency of their mRNA targets. Several evidences suggest that they play a role in tumorigenesis. So far, all types of thyroid tumors have been studied for miRNA expression except autonomous adenomas (AA), benign tumors characterized by the constitutive activation of the cAMP-dependent pathway, leading to a functional hyperactivity of the tissues. The objective of the study was to identify the deregulated miRNA in AA and to correlate the data with mRNA regulation observed in the same samples. AA and their corresponding adjacent tissues were hybridized on miRNA and mRNA microarrays. In order to investigate the correlation between both datasets and to identify mRNA regulations, bioinformatic mRNA target prediction softwares were used. 12 miRNAs were found as downregulated and 1 as upregulated in the tumors. Members of 3 different miR-families (miR-19, miR-29 and miR-135 families) were found among the regulated miRNA. By bioinformatic predictions we searched, among the mRNA microarray data, for regulated mRNA which could be targeted by the modulated miRNA. A great enrichment in mRNA encoding proteins involved in the extracellular matrix organization, as well as different phosphodiesterases were identified among the putative targets. The global miRNA profiles are not greatly modified, confirming the definition of these tumors as minimal deviation tumors. These results support a role for miRNA in ECM regulation and tissue remodelling occurring during tumor development, as well as in the retrocontrol of the activated cAMP pathway. Overall design: 7 tumors hybridized in dey-swap, compared to thier adjacent normal tissues.MicroRNA（miRNA）是一类小型非编码RNA，可调控靶信使RNA（mRNA）的稳定性与翻译效率。多项研究证据表明，其在肿瘤发生过程中发挥重要作用。截至目前，除自主性腺瘤（AA）外，所有类型的甲状腺肿瘤的miRNA表达谱均已被研究；自主性腺瘤是一类因cAMP依赖通路组成性激活而导致组织功能亢进的良性肿瘤。本研究旨在鉴定自主性腺瘤中失调的miRNA，并将所得数据与同一样本中观测到的mRNA调控情况进行关联分析。研究团队将自主性腺瘤及其对应癌旁组织分别在miRNA与mRNA微阵列上进行杂交实验。为探究两组数据集间的关联并鉴定mRNA调控事件，研究人员使用了生物信息学mRNA靶标预测软件。结果显示，肿瘤组织中共有12种miRNA表达下调，1种miRNA表达上调。受调控的miRNA分属3个不同的miRNA家族（miR-19家族、miR-29家族与miR-135家族）。通过生物信息学预测，研究人员在mRNA微阵列数据中筛选可被上述失调miRNA靶向的差异表达mRNA。最终在候选靶标中发现，大量编码参与细胞外基质（extracellular matrix, ECM）组织相关蛋白的mRNA，以及多种磷酸二酯酶的mRNA显著富集。整体miRNA表达谱并未发生显著改变，这印证了此类肿瘤属于“微小偏离型肿瘤”的定义。本研究结果支持miRNA在肿瘤发生过程中ECM调控与组织重塑，以及对激活的cAMP依赖通路的逆向调控中发挥作用的结论。总体实验设计：7例肿瘤样本采用dey-swap杂交方式，与对应癌旁正常组织进行比较。