Homeodomain Transcription Factors Nkx2.2 and Pax6 as Novel Biomarkers for Meningioma Tumor Treatment.

IF 0.9 Q3 DEMOGRAPHY

Immigrants and Minorities Pub Date : 2024-01-01 Epub Date: 2022-08-30 DOI:10.1007/s12291-022-01085-1

Shirin Farheen, Mubeena Mariyath Pm, Suhailur Rehman, Md Fakhrul Hoda, Yakhlesh Gupta, Asif Ali, Kunzang Chosdol, Mehdi H Shahi

{"title":"Homeodomain Transcription Factors Nkx2.2 and Pax6 as Novel Biomarkers for Meningioma Tumor Treatment.","authors":"Shirin Farheen, Mubeena Mariyath Pm, Suhailur Rehman, Md Fakhrul Hoda, Yakhlesh Gupta, Asif Ali, Kunzang Chosdol, Mehdi H Shahi","doi":"10.1007/s12291-022-01085-1","DOIUrl":null,"url":null,"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.Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01085-1.","PeriodicalId":51940,"journal":{"name":"Immigrants and Minorities","volume":"15 1","pages":"47-59"},"PeriodicalIF":0.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10784245/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immigrants and Minorities","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s12291-022-01085-1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/8/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"DEMOGRAPHY","Score":null,"Total":0}

引用次数: 0

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.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01085-1.

查看原文本刊更多论文

作为脑膜瘤治疗新生物标志物的同源基因转录因子 Nkx2.2 和 Pax6

脑膜瘤是一种常见的脑肿瘤，目前尚无特异性检测和治疗方法。音速刺猬（Shh）细胞信号通路是哺乳动物器官发生和肿瘤发生（包括脑膜瘤）的重要调节通路。Shh细胞信号通路通过主要转录因子Gli1发挥级联功能，其下游的Pax6和Nkx2.2进一步对其进行调控。本研究旨在探讨脑膜瘤样本中Sonic hedgehog-Gli1细胞信号通路的调控及其潜在的下游靶点。本研究共使用了 24 例手术切除的脑膜瘤样本，使用电子显微镜技术、苏木精和伊红以及 DAPI 染色评估细胞学变化。免疫组化法测定了 Gli1、Nkx2.2 和 Pax6 转录因子的表达模式。采用 RT-qPCR 方法评估 mRNA 的表达。随后，使用 amploseq 技术对样本进行了全转录组分析。结果与正常人脑组织（或正常脑膜）的结果进行了比较。与正常人的脑组织相比，脑膜瘤样本的细胞核拥挤，形态发生变化。转录因子Nkx2.2在所有样本中均有高表达（24/24，100%）。24 个脑膜瘤中有 21 个（88%）显示 Gli1 和 Pax6 高表达。对两个脑膜瘤样本进行的全转录组分析也显示，与正常对照组相比，脑膜瘤样本中的 Gli1 表达信号非常高。因此，我们可以得出结论：Shh-Gli1通路在脑膜瘤细胞中被异常激活，并上调转录因子Pax6和Nkx2.2的表达：在线版本包含补充材料，可查阅 10.1007/s12291-022-01085-1。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Immigrants and Minorities DEMOGRAPHY-

CiteScore

1.20

自引率

0.00%

发文量

期刊介绍： Immigrants & Minorities, founded in 1981, provides a major outlet for research into the history of immigration and related studies. It seeks to deal with the complex themes involved in the construction of "race" and with the broad sweep of ethnic and minority relations within a historical setting. Its coverage is international and recent issues have dealt with studies on the USA, Australia, the Middle East and the UK. The journal also supports an extensive review section.