The impact of MEIS1 TALE homeodomain transcription factor knockdown on glioma stem cell growth.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI:10.1080/19768354.2024.2327340

Hyun-Jin Kim, Don Carlo Batara, Young-Jun Jeon, Seongsoo Lee, Samuel Beck, Sung-Hak Kim

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Abstract

Myeloid ecotropic virus insertion site 1 (MEIS1) is a HOX co-factor necessary for organ development and normal hematopoiesis. Recently, MEIS1 has been linked to the development and progression of various cancers. However, its role in gliomagenesis particularly on glioma stem cells (GSCs) remains unclear. Here, we demonstrate that MEIS1 is highly upregulated in GSCs compared to normal, and glioma cells and to its differentiated counterparts. Inhibition of MEIS1 expression by shRNA significantly reduced GSC growth in both in vitro and in vivo experiments. On the other hand, integrated transcriptomics analyses of glioma datasets revealed that MEIS1 expression is correlated to cell cycle-related genes. Clinical data analysis revealed that MEIS1 expression is elevated in high-grade gliomas, and patients with high MEIS1 levels have poorer overall survival outcomes. The findings suggest that MEIS1 is a prognostic biomarker for glioma patients and a possible target for developing novel therapeutic strategies against GBM.

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MEIS1 TALE同源转录因子敲除对胶质瘤干细胞生长的影响

髓系生态病毒插入位点1（MEIS1）是器官发育和正常造血所必需的HOX辅助因子。最近，MEIS1 与多种癌症的发生和发展有关。然而，它在胶质瘤发生中的作用，尤其是对胶质瘤干细胞（GSCs）的作用仍不清楚。在这里，我们证明了与正常细胞和胶质瘤细胞相比，MEIS1在胶质瘤干细胞及其分化的对应细胞中高度上调。在体外和体内实验中，通过 shRNA 抑制 MEIS1 的表达可显著降低 GSC 的生长。另一方面，胶质瘤数据集的综合转录组学分析表明，MEIS1的表达与细胞周期相关基因有关。临床数据分析显示，MEIS1在高级别胶质瘤中表达升高，MEIS1水平高的患者总生存率较低。研究结果表明，MEIS1是胶质瘤患者的预后生物标志物，也是开发针对GBM的新型治疗策略的可能靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464