Pleuropulmonary blastoma (PPB) is a very rare pediatric lung disease. It can progress from abnormal epithelial cysts to an aggressive sarcoma with poor survival. PPB diagnosis is difficult as it can be confounded with other cystic lung disorders like congenital pulmonary airway malformations (CPAM). PPB is associated with mutations in DICER1 that perturb the microRNA (miRNA) profile in lung. How DICER1 and miRNAs act during PPB pathogenesis remains unsolved. Lung epithelial deletion of the Yin Yang1 (Yy1) gene in mice causes a phenotype mimicking the cystic form of PPB and it affects the expression of key regulators of lung development. Similar changes in expression were observed in PPB but not in CPAM lung biopsies, revealing a distinctive PPB molecular signature. Deregulation of molecules promoting epithelial-mesenchymal transition (EMT) was detected in PPB specimens suggesting that EMT might participate in tumor progression. Changes in miRNA expression also occurred in PPB lung biopsies. miR-125a-3p, a candidate to regulate YY1 expression and lung branching, was abnormally highly expressed in PPB samples. Together, these findings support the concept that reduced expression of YY1, due to the abnormal miRNA profile ensuing DICER1 mutations, contributes to PPB development via its impact on the expression of key lung developmental genes.

中文翻译：

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小鼠肺上皮中 Yy1 的缺失揭示了控制胸膜肺母细胞瘤发病机制的分子机制。

胸膜肺母细胞瘤（PPB）是一种非常罕见的小儿肺部疾病。它可以从异常上皮囊肿进展为存活率低的侵袭性肉瘤。PPB 的诊断很困难，因为它可能与其他囊性肺疾病（如先天性肺气道畸形 (CPAM)）混淆。PPB 与DICER1突变相关，该突变会扰乱肺部的 microRNA (miRNA) 谱。DICER1和 miRNA 在 PPB 发病机制中如何发挥作用仍未解决。小鼠肺上皮的Yin Yang1 ( Yy1 ) 基因缺失会导致模仿 PPB 囊性形式的表型，并影响肺发育关键调节因子的表达。在 PPB 中观察到类似的表达变化，但在 CPAM 肺活检中没有观察到，揭示了独特的 PPB 分子特征。在 PPB 样本中检测到促进上皮间质转化 (EMT) 的分子失调，表明 EMT 可能参与肿瘤进展。PPB 肺活检中也发生了 miRNA 表达的变化。miR-125a-3p 是调节YY1表达和肺分支的候选者，在 PPB 样本中异常高表达。总之，这些发现支持这样的概念：由于DICER1突变导致的异常 miRNA 谱，YY1 表达减少，通过影响关键肺发育基因的表达，有助于 PPB 发育。