Defects in achieving a fully differentiated state and aberrant expression of genes and microRNAs (miRs) involved in differentiation are common to virtually all tumor types. Here, we demonstrate that the zinc finger transcription factor ZNF281/Zfp281 is down-regulated during epithelial, muscle, and granulocytic differentiation in vitro. The expression of this gene is absent in terminally differentiated human tissues, in contrast to the elevated expression in proliferating/differentiating ones. Analysis of the 3'UTR of ZNF281/Zfp281 revealed the presence of numerous previously undescribed miR binding sites that were proved to be functional for miR-mediated post-transcriptional regulation. Many of these miRs are involved in differentiation pathways of distinct cell lineages. Of interest, ZNF281/Zfp281 is able to inhibit muscle differentiation promoted by miR-1, of which ZNF281/Zfp281 is a direct target. These data suggest that down-regulation of ZNF281/Zfp281 during differentiation in various cell types may occur through specific miRs whose expression is tissue-restricted. In addition, we found that in rhabdomyosarcoma and leiomyosarcoma tumors, the expression of ZNF281/Zfp281 is significantly higher compared with normal counterparts. We extended our analysis to other human soft tissue sarcomas, in which the expression of ZNF281 is associated with a worse prognosis. In summary, we highlight here a new role of ZNF281/Zfp281 in counteracting muscle differentiation; its down-regulation is at least in part mediated by miR-1. The elevated expression of ZNF281/Zfp281 in soft tissue sarcomas warrants further analysis for its possible exploitation as a prognostic marker in this class of tumors.

中文翻译：

---

ZNF281 / Zfp281是miR-1的靶标，可抵消肌肉分化。

几乎所有类型的肿瘤都存在达到完全分化状态的缺陷以及参与分化的基因和微小RNA（miR）异常表达的缺陷。在这里，我们证明锌指转录因子ZNF281 / Zfp281在上皮，肌肉和粒细胞分化过程中被下调。该基因的表达在终末分化的人类组织中不存在，这与增殖/分化的组织中的表达升高相反。对ZNF281 / Zfp281的3'UTR的分析表明，存在许多先前未描述的miR结合位点，这些位点被证明对miR介导的转录后调控具有功能。这些miR中的许多都参与不同细胞谱系的分化途径。出于兴趣，ZNF281 / Zfp281能够抑制miR-1促进的肌肉分化，其中ZNF281 / Zfp281是直接靶标。这些数据表明，在各种细胞类型的分化过程中，ZNF281 / Zfp281的下调可能是通过表达受组织限制的特定miR引起的。此外，我们发现在横纹肌肉瘤和平滑肌肉瘤中，ZNF281 / Zfp281的表达明显高于正常人。我们将分析扩展到其他人的软组织肉瘤，其中ZNF281的表达与更差的预后相关。总而言之，我们在这里重点介绍ZNF281 / Zfp281在抵消肌肉分化中的新作用。其下调至少部分由miR-1介导。