GBP2 是皮肤黑色素瘤的有利预后标志物，并通过 Wnt/β-catenin 通路影响其进展。

GBP2 Is a Favorable Prognostic Marker of Skin Cutaneous Melanoma and Affects Its Progression via the Wnt/β-catenin Pathway.

机构信息

Department of Burn and Plastic Surgery, Taizhou People's Hospital, Taizhou, China.

Tai Zhou University, Taizhou, China.

出版信息

Ann Clin Lab Sci. 2021 Nov;51(6):772-782.

PMID:34921030

Abstract

OBJECTIVE

Skin cutaneous melanoma (SKCM) is a common cutaneous malignant tumour. This study explored the expression and the downstream regulation mechanism of guanylate binding protein 2 (GBP2), an interferon (IFN)-induced protein, in SKCM.

METHODS

Western blot was employed to verify the expression of SBP2 and its downstream Wnt/β-catenin pathway-related proteins. We studied the relationship between GBP2 and the SKCM prognosis through database analysis. , gain-and-loss-of function experiments were conducted in SKCM cells. Cell viability was monitored by the cell counting kit-8 (CCK8) assay, the colony formation assay detected cell proliferation, and apoptosis was verified by flow cytometry. Transwell assay was conducted to test cell invasion and migration, while Western blot was employed to monitor the epithelial-mesenchymal transition (EMT) of SKCM cells.

RESULTS

The GBP2 expression in SKCM cells and tissues was lower than normal cells and tissues. GBP2 overexpression inhibited SKCM cell proliferation, migration, invasion, and EMT and promoted cell apoptosis. In contrast, the GBP2 knockdown had the reverse effect. Mechanically, Wnt/β-catenin was inactivated by GBP2 overexpression and was enhanced by GBP2 knockdown. Drug activation of Wnt/β-catenin significantly attenuated the malignant phenotypic inhibition induced by GBP2 up-regulation in SKCM cells.

CONCLUSION

GBP2 exerts anti-tumour effects by inhibiting the Wnt/β-catenin pathway in SKCM and is related to a favourable prognosis.

摘要

目的

皮肤黑色素瘤（SKCM）是一种常见的皮肤恶性肿瘤。本研究探讨了干扰素（IFN）诱导蛋白鸟苷酸结合蛋白 2（GBP2）在 SKCM 中的表达及其下游调控机制。

方法

采用 Western blot 验证 SBP2 及其下游 Wnt/β-catenin 通路相关蛋白的表达。通过数据库分析研究 GBP2 与 SKCM 预后的关系。在 SKCM 细胞中进行增益和缺失功能实验。通过细胞计数试剂盒-8（CCK8）检测细胞活力，集落形成实验检测细胞增殖，流式细胞术验证细胞凋亡。Transwell 实验检测细胞侵袭和迁移，Western blot 检测 SKCM 细胞上皮-间充质转化（EMT）。

结果

GBP2 在 SKCM 细胞和组织中的表达低于正常细胞和组织。GBP2 过表达抑制 SKCM 细胞增殖、迁移、侵袭和 EMT，并促进细胞凋亡。相反，GBP2 敲低则具有相反的效果。机制上，GBP2 过表达使 Wnt/β-catenin 失活，而 GBP2 敲低则增强。Wnt/β-catenin 的药物激活显著减弱了 GBP2 上调在 SKCM 细胞中诱导的恶性表型抑制作用。