Abstract:
Meningioma is a common brain tumour which has neither a specific detection nor treatment method. The Sonic hedgehog (Shh) cell signaling pathway is a crucial regulatory pathway of mammalian organogenesis and tumorigenesis including meningioma. Shh cell signalling pathway cascade function by main transcription factor Gli1 and which further regulates in its downstream to Pax6 and Nkx2.2. This current study is aimed to explore the regulation of the Sonic hedgehog-Gli1 cell signaling pathway and its potential downstream targets in meningioma samples. A total of 24 surgically resected meningioma samples were used in this current study.Cytological changes were assessed using electron microscopic techniques as well as hematoxylin & eosin and DAPI staining. The expression pattern of Gli1, Nkx2.2 and Pax6 transcription factors were determined by using immunohistochemistry. The mRNA expression was assessed using RT-qPCR assays. Later, the whole transcriptome analysis of samples was performed with the amploseq technique. Results were compared with those obtained in normal human brain tissue (or normal meninges). Compared to the normal human brain tissue, meningioma samples showed crowded nuclei with morphological changes. Transcription factor Nkx2.2 expressed highly in all samples (24/24, 100%). Twenty-one of the 24 meningiomas (88%) showed high Gli1 and Pax6 expression. Whole transcriptome analysis of two meningioma samples also exhibited a very high increase in Gli1 expression signal in meningioma samples as compare to normal control. Hence, we may conclude that the Shh-Gli1 pathway is aberrantly activated in meningioma cells and is canonically upregulating the expression of transcription factors Pax6 and Nkx2.2.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12291-022-01085-1.
摘要:
脑膜瘤是一种常见的脑肿瘤,既没有特定的检测方法,也没有治疗方法。Sonichedgehog(Shh)细胞信号传导途径是哺乳动物器官发生和包括脑膜瘤在内的肿瘤发生的关键调节途径。Shh细胞信号通路通过主要转录因子Gli1级联功能,并在其下游进一步调节Pax6和Nkx2.2。本研究旨在探索Sonichedgehog-Gli1细胞信号通路及其潜在下游靶标在脑膜瘤样本中的调控。本研究共使用24例手术切除的脑膜瘤样品。使用电子显微镜技术以及苏木精和伊红和DAPI染色评估细胞学变化。免疫组织化学检测Gli1、Nkx2.2和Pax6转录因子的表达模式。使用RT-qPCR测定法评估mRNA表达。稍后,使用amploseq技术对样本进行全转录组分析.将结果与正常人脑组织(或正常脑膜)中获得的结果进行比较。与正常人的脑组织相比,脑膜瘤样本显示出拥挤的细胞核,并有形态学变化。转录因子Nkx2.2在所有样品中高度表达(24/24,100%)。24例脑膜瘤中有21例(88%)显示高Gli1和Pax6表达。与正常对照相比,两个脑膜瘤样品的全转录组分析也显示脑膜瘤样品中Gli1表达信号的非常高的增加。因此,我们可以得出结论,Shh-Gli1途径在脑膜瘤细胞中被异常激活,并且正在典型地上调转录因子Pax6和Nkx2.2的表达。
■在线版本包含补充材料,可在10.1007/s12291-022-01085-1获得。