The miR-192-EGR1/HOXB9 Loop Regulates Glioma Cell Stemness and Malignant Phenotypes by Promoting Their Mesenchymal Transition

IF 4.2
Guo-Wei Li, Yan-Ping Jin, Min-Feng Sheng
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Abstract

To clarify the regulatory effects of miR-192 on the malignant phenotypes of glioma cells. We used PCR, WB and immunofluorescence to detect regulatory factors in glioma samples. Then, we chose lentiviral plasmid transfection to construct cell models. We used CCK-8 and colony formation to evaluate the proliferation ability of these cells and used Transwell/scratch tests to evaluate their invasion ability. CD133-expressing GSCs were observed under a microscope, and their stemness properties were evaluated. We constructed a tumour-bearing model via subcutaneous inoculation. Tumour growth curves and tumour weights were determined subsequently. The proteins involved in the miR-192-EGR1/HOXB9 loop were evaluated via IHC staining. MiR-192 was significantly reduced in glioma samples, and this factor downregulated EGR1 and HOXB9 via targeted binding, thus forming a semi-open loop. Moreover, the proliferation, invasion and migration of glioma cells overexpressing miR-192 were significantly decreased. These malignant phenotypes were abrogated completely with EGR1 or HOXB9 overexpression. Similarly, these changes were essentially consistent with MT marker expression and the stem-like properties in glioma cells. Meanwhile, miR-192 inhibits the tumorigenesis of glioma cells via the EGR1-HOXB9 loop. MiR-192 could inhibit MT in glioma cells through the EGR1-HOXB9 loop. Thus, it reduces their stemness and abrogates their malignant phenotypes.

Abstract Image

miR-192-EGR1/HOXB9环通过促进胶质瘤细胞间质转化调节胶质瘤细胞干性和恶性表型
阐明miR-192对胶质瘤细胞恶性表型的调控作用。我们采用PCR、WB和免疫荧光检测胶质瘤样本中的调节因子。然后,我们选择慢病毒质粒转染构建细胞模型。我们用CCK-8和集落形成法评价这些细胞的增殖能力,用Transwell/scratch法评价它们的侵袭能力。在显微镜下观察表达cd133的GSCs,并评价其干性。我们通过皮下接种建立了荷瘤模型。随后测定肿瘤生长曲线和肿瘤重量。通过免疫组化染色评估miR-192-EGR1/HOXB9环中涉及的蛋白。MiR-192在胶质瘤样本中显著降低,该因子通过靶向结合下调EGR1和HOXB9,形成半开环。此外,过表达miR-192的胶质瘤细胞的增殖、侵袭和迁移能力显著降低。这些恶性表型被EGR1或HOXB9过表达完全消除。同样,这些变化与胶质瘤细胞的MT标记物表达和干细胞样特性基本一致。同时,miR-192通过EGR1-HOXB9环抑制胶质瘤细胞的肿瘤发生。MiR-192可以通过EGR1-HOXB9环抑制胶质瘤细胞中的MT。因此,它减少了它们的干性并消除了它们的恶性表型。
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来源期刊
CiteScore
11.50
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0.00%
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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