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整合素 α3 通过调控 POU3F2 介导脑胶质瘤干细胞特性和侵袭

Integrin α3 Mediates Stemness and Invasion of Glioblastoma by Regulating POU3F2.

机构信息

Department of Neurosurgery, Cangzhou Central Hospital, Xinhua West Road, Cangzhou, 061000, Hebei, China.

出版信息

Curr Protein Pept Sci. 2023;24(3):247-256. doi: 10.2174/1389203724666230224115459.

DOI:10.2174/1389203724666230224115459
PMID:36843258
Abstract

BACKGROUND

Glioblastoma (GBM) is an aggressive brain tumor. Integrins have been implicated in the malignancy of GBM. A recent study demonstrated that integrin α3 (ITGA3) promoted the invasion of breast cancer cells by regulating transcriptional factor POU3F2. However, whether this also happened in GBM remained unknown.

METHODS

Therefore, we explored the relationship between ITGA3 and POU3F2 in GBM. We measured the expression of ITGA3 and POU3F2 in GBM tissues. We generated ITGA3 knockdown and POU3F2 knockdown GBM U87MG cells and the proliferation, migration and invasion, the expression of stemness markers and epithelial to mesenchymal transition (EMT) markers were measured. We transplanted ITGA3 knockdown and POU3F2 knockdown GBM U87MG cells into mice. The mice were treated with anti-ITGA3 antibody. The tumor sizes, the expression of stemness markers and epithelial-to-mesenchymal transition (EMT) markers were measured.

RESULTS

Both ITGA3 and POU3F2 were upregulated in GBM tissues. Knocking down ITGA3 resulted in reduced expression of POU3F2. Knocking down ITGA3 and POU3F2 suppressed U87MG cells proliferation, migration and invasion, inhibited the expression of stemness markers and prevented epithelial- to-mesenchymal transition. The transplantation of ITGA3 knockdown and POU3F2 knockdown U87MG cells decreased tumor size.

CONCLUSION

Anti-ITGA3 antibody treatment reduced the tumor size. ITGA3 regulates stemness and invasion of glioblastoma through POU3F2.

摘要

背景

胶质母细胞瘤(GBM)是一种侵袭性脑肿瘤。整合素已被牵涉到 GBM 的恶性肿瘤中。最近的一项研究表明,整合素α3(ITGA3)通过调节转录因子 POU3F2 促进乳腺癌细胞的侵袭。然而,这种情况是否也发生在 GBM 中尚不清楚。

方法

因此,我们探讨了 ITGA3 和 POU3F2 在 GBM 中的关系。我们测量了 GBM 组织中 ITGA3 和 POU3F2 的表达。我们生成了 ITGA3 敲低和 POU3F2 敲低的 GBM U87MG 细胞,并测量了增殖、迁移和侵袭、干性标志物和上皮间质转化(EMT)标志物的表达。我们将 ITGA3 敲低和 POU3F2 敲低的 GBM U87MG 细胞移植到小鼠体内。用抗 ITGA3 抗体处理小鼠。测量肿瘤大小、干性标志物和上皮间质转化(EMT)标志物的表达。

结果

ITGA3 和 POU3F2 在 GBM 组织中均上调。敲低 ITGA3 导致 POU3F2 表达降低。敲低 ITGA3 和 POU3F2 抑制了 U87MG 细胞的增殖、迁移和侵袭,抑制了干性标志物的表达,并阻止了上皮-间质转化。ITGA3 敲低和 POU3F2 敲低 U87MG 细胞的移植降低了肿瘤体积。

结论

抗 ITGA3 抗体治疗降低了肿瘤体积。ITGA3 通过 POU3F2 调节胶质母细胞瘤的干性和侵袭。

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