Floor Sébastien L, Hebrant Aline, Pita Jaime M, Saiselet Manuel, Trésallet Christophe, Libert Frederick, Andry Guy, Dumont Jacques E, van Staveren Wilma C, Maenhaut Carine
Institute of Interdisciplinary Research (IRIBHM), Free University of Brussels (ULB), Brussels, Belgium.
Pitié-Salpêtrière Hospital, Université Pierre et Marie Curie, Paris, France.
PLoS One. 2014 Nov 6;9(11):e111581. doi: 10.1371/journal.pone.0111581. eCollection 2014.
For thyroid tumorigenesis, two main human in vitro models are available: primary cultures of human thyrocytes treated with TSH or EGF/serum as models for autonomous adenomas (AA) or papillary thyroid carcinomas (PTC) respectively, and human thyroid tumor derived cell lines. Previous works of our group have assessed properties of those models, with a special emphasis on mRNA regulations. It is often assumed that miRNA may be one of the primary events inducing these mRNA regulations.
The purpose of this study was to investigate the representativity of those models to study microRNA regulations and their relation with mRNA expression. To achieve this aim, the miRNA expressions profiles of primary cultures treated with TSH or EGF/serum and of 6 thyroid cancer cell lines were compared to the expression profiles of 35 tumor tissues obtained by microarrays.
Our data on primary cultures have shown that the TSH or EGF/serum treatment did not greatly modify the microRNA expression profiles, which is contrary to what is observed for mRNA expression profiles, although they still evolved differently according to the treatment. The analysis of miRNA and mRNA expressions profiles in the cell lines has shown that they have evolved into a common, dedifferentiated phenotype, closer to ATC than to the tumors they are derived from.
Long-terms TSH or EGF/serum treatments do not mimic AA or PTC respectively in terms of miRNA expression as they do for mRNA, suggesting that the regulations of mRNA expression induced by these physiological agents occur independently of miRNA. The general patterns of miRNA expression in the cell lines suggest that they represent a useful model for undifferentiated thyroid cancer. Mirna probably do not mediate the rapid changes in gene expression in rapid cell biology regulation.
对于甲状腺肿瘤发生，有两种主要的人类体外模型：分别用促甲状腺激素（TSH）或表皮生长因子（EGF）/血清处理人甲状腺细胞的原代培养物，作为自主性腺瘤（AA）或甲状腺乳头状癌（PTC）的模型，以及人甲状腺肿瘤来源的细胞系。我们小组之前的工作评估了这些模型的特性，特别关注mRNA调控。人们通常认为，微小RNA（miRNA）可能是诱导这些mRNA调控的主要事件之一。
本研究的目的是调查这些模型在研究miRNA调控及其与mRNA表达关系方面的代表性。为实现这一目标，将用TSH或EGF/血清处理的原代培养物以及6种甲状腺癌细胞系的miRNA表达谱与通过微阵列获得的35个肿瘤组织的表达谱进行比较。
我们关于原代培养物的数据表明，TSH或EGF/血清处理并没有极大地改变miRNA表达谱，这与mRNA表达谱的情况相反，尽管它们仍根据处理方式而有不同变化。对细胞系中miRNA和mRNA表达谱的分析表明，它们已演变成一种共同的去分化表型，更接近未分化甲状腺癌（ATC）而非其来源的肿瘤。
长期的TSH或EGF/血清处理在miRNA表达方面分别不像在mRNA方面那样模拟AA或PTC，这表明这些生理因子诱导的mRNA表达调控独立于miRNA发生。细胞系中miRNA表达的一般模式表明它们代表了未分化甲状腺癌的有用模型。miRNA可能不介导快速细胞生物学调控中基因表达的快速变化。
