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转录因子PU.1参与胶质瘤的进展。

Transcription factor PU.1 is involved in the progression of glioma.

作者信息

Xu Yuanzhi, Gu Song, Bi Yunke, Qi Xiangqian, Yan Yujin, Lou Meiqing

机构信息

Department of Neurosurgery, Shanghai First People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, P.R. China.

Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

出版信息

Oncol Lett. 2018 Mar;15(3):3753-3759. doi: 10.3892/ol.2018.7766. Epub 2018 Jan 10.

Abstract

Glioma is a severe disease of the central nervous system. Although previous studies have identified the important role of the immune response in association with tumor intervention, it is still unknown whether PU.1, a transcription factor known for its role in myeloid differentiation and immune responses, is involved in the progression of glioma. In the present study, we found a significant increase in SPI1, the gene that encodes PU.1, in samples from patients with glioma. Through genotype-phenotype association analysis several candidate factors that may mediate the role of PU.1 in glioma were identified. To further validate the association between PU.1 and glioma we found that the expression of BTK, a potential target of PU.1, was also upregulated in patients with glioma. We also demonstrated that various biological pathways could be involved in PU.1-associated glioma by analyzing these potential targets in the Reactome database. These results provide evidence that PU.1 could serve a role in the progress of glioma through its transcriptional targets in multiple signaling pathways. Therefore, in addition to its role in hematopoietic linage development and leukemia, PU.1 appears to be involved in the regulation of glioma and potentially in other malignant cancers.

摘要

神经胶质瘤是一种严重的中枢神经系统疾病。尽管先前的研究已经确定免疫反应在肿瘤干预中的重要作用,但对于以其在髓系分化和免疫反应中的作用而闻名的转录因子PU.1是否参与神经胶质瘤的进展仍不清楚。在本研究中,我们发现编码PU.1的基因SPI1在神经胶质瘤患者的样本中有显著增加。通过基因型-表型关联分析,确定了几个可能介导PU.1在神经胶质瘤中作用的候选因子。为了进一步验证PU.1与神经胶质瘤之间的关联,我们发现PU.1的潜在靶点BTK在神经胶质瘤患者中的表达也上调。通过在Reactome数据库中分析这些潜在靶点,我们还证明了多种生物学途径可能参与了与PU.1相关的神经胶质瘤。这些结果提供了证据,表明PU.1可以通过其在多个信号通路中的转录靶点在神经胶质瘤进展中发挥作用。因此,除了其在造血谱系发育和白血病中的作用外,PU.1似乎还参与神经胶质瘤的调控,并可能参与其他恶性肿瘤的调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c1/5795926/3f0220e0fb1a/ol-15-03-3753-g00.jpg

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