Herein, we assess the gene expression changes activated in thyroid tumors through a computational approach, using the MapReduce algorithm. Through this predictive analysis, we identified the TfR1 gene as a critical mediator of thyroid tumor progression. Then, we investigated the effect of TfR1 gene silencing through small interfering RNA (siRNA) in the expression of extracellular signal-regulated kinase 1/2 (Erk1/2) pathway and c-Myc in human differentiated follicular and undifferentiated anaplastic thyroid cancer. The expression levels of cyclin D₁, p53, and p27, proteins involved in cell cycle progression, were also evaluated. The effect of TfR1 gene silencing through siRNA on the apoptotic pathway activation was also tested. Computational prediction and in vitro studies demonstrate that TfR1 plays a key role in thyroid cancer and that its downregulation was able to inhibit the ERK pathway, reducing also c-Myc expression, which blocks the cell cycle and activates the apoptotic pathway. We demonstrate that TfR1 plays a crucial role for a rapid and transient activation of the ERK signaling pathway, which induces a deregulation of genes involved in the aberrant accumulation of intracellular free iron and in drug resistance. We also suggest that TfR1 might represent an important target for thyroid cancer therapy.

在本文中，我们使用MapReduce算法通过计算方法评估了在甲状腺肿瘤中激活的基因表达变化。通过这种预测分析，我们确定了TfR1基因是甲状腺肿瘤进展的关键介质。然后，我们研究了通过小分子干扰RNA（siRNA）抑制TfR1基因在人分化的滤泡性和未分化性间变性甲状腺癌中细胞外信号调节激酶1/2（Erk1 / 2）通路和c-Myc表达的作用。还评估了细胞周期蛋白参与的细胞周期蛋白D ₁，p53和p27的表达水平。还测试了通过siRNA沉默的TfR1基因对凋亡途径激活的影响。计算预测与体外研究表明，TfR1在甲状腺癌中起关键作用，其下调能够抑制ERK途径，同时降低c-Myc表达，从而阻断细胞周期并激活凋亡途径。我们证明，TfR1在ERK信号通路的快速和短暂激活中起着至关重要的作用，该信号通路诱导了参与细胞内游离铁异常积累和耐药性的基因的失调。我们还建议TfR1可能代表甲状腺癌治疗的重要目标。