PRDX2 敲低抑制体外培养尤文肉瘤细胞的增殖、生长、迁移、侵袭和 MMP9 活性。

Knockdown of PRDX2 Inhibits the Proliferation, Growth, Migration, Invasion, and MMP9 Activity of Ewing's Sarcoma Cells Cultured In Vitro.

机构信息

Department of Bone and Soft Tissue Tumors, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, Beijing, China.

Institute of Analysis and Testing, Beijng Academy of Science and Technology (Beijing Center for Physical & Chemical Analysis), Beijing, China.

出版信息

Cancer Rep (Hoboken). 2024 Sep;7(9):e2122. doi: 10.1002/cnr2.2122.

DOI:10.1002/cnr2.2122

PMID:39234629

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11375325/

Abstract

BACKGROUND

Ewing's sarcoma (ES) is the second most common malignant primary bone tumor in children and adolescents. Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme.

AIMS

Here, we investigated the role and mechanism of PRDX2 in the development of ES.

METHODS AND RESULTS

PRDX2 expression was knocked down in A673 and RDES cells by specific siRNA interference (si-PRDX2). Knockdown of PRDX2 strongly inhibited the proliferation, growth, migration, invasion, and MMP9 activity and induces apoptosis of A673 and RDES cells. si-PRDX2 significantly inhibited the phosphorylation of Akt and the expression of cyclin D1. The transcription factor that might regulate PRDX2 transcription was predicted with the JASPAR and UCSC databases, and analyzed using dual-luciferase and Chromatin co-immunoprecipitation experiments. SNAI1 could activate the transcription of PRDX2 by binding to predicted promoter binding site.

CONCLUSION

PRDX2 may be a potential therapeutic target for ES.

摘要

背景

尤文氏肉瘤（ES）是儿童和青少年中第二常见的恶性原发性骨肿瘤。过氧化物酶 2（PRDX2）是一种抗氧化酶。

目的

本研究旨在探讨 PRDX2 在 ES 发展中的作用和机制。

方法和结果

通过特异性 siRNA 干扰（si-PRDX2）下调 A673 和 RDES 细胞中的 PRDX2 表达。PRDX2 下调强烈抑制 A673 和 RDES 细胞的增殖、生长、迁移、侵袭和 MMP9 活性，并诱导细胞凋亡。si-PRDX2 显著抑制 Akt 的磷酸化和细胞周期蛋白 D1 的表达。使用 JASPAR 和 UCSC 数据库预测可能调节 PRDX2 转录的转录因子，并通过双荧光素酶和染色质共免疫沉淀实验进行分析。SNAI1 可以通过结合预测的启动子结合位点激活 PRDX2 的转录。