Small interfering RNA-induced silencing of galectin-3 inhibits the malignant phenotypes of osteosarcoma in vitro (Retracted Article)
Small interfering RNA-induced silencing of galectin-3 inhibits the malignant phenotypes of osteosarcoma in vitro (Retracted Article)
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DOI：
10.3892/mmr.2015.4165
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发表时间：
2015-10-01
影响因子：
3.4
通讯作者：
Liao, Zhan
中科院分区：
文献类型：
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作者：
Lei, Pengfei;He, Hongbo;Liao, Zhan
骨肉瘤（osteosarcoma，OS）是最常见的骨恶性肿瘤。最近已经证明半乳糖凝集素-3（一种多功能β-半乳糖苷结合物）在OS组织中显著上调，并且与其进展和转移相关。然而，半乳糖凝集素-3在OS细胞中的细胞生物学过程的调节中的详细作用仍有待阐明。本研究报道了半乳糖凝集素-3的mRNA和蛋白水平在OS组织中与其匹配的正常相邻组织相比显著增加。此外，与人成骨细胞系hFOB 1.19相比，半乳糖凝集素-3在三种OS细胞系Saos-2、MG 63和U2 OS中上调。通过半乳糖凝集素-3特异性小干扰RNA敲低半乳糖凝集素-3显著抑制OS细胞增殖并诱导细胞凋亡。此外，半乳糖凝集素-3表达的沉默显着抑制OS细胞的迁移和侵袭，伴随着基质金属蛋白酶2和-9的蛋白表达的显着下降。机制研究表明，丝裂原活化蛋白激酶激酶/细胞外信号调节蛋白激酶信号通路可能参与半乳糖凝集素3介导的OS细胞侵袭。总之，本研究首次报道了半乳糖凝集素-3沉默抑制骨肉瘤的恶性表型。因此，galectin-3可能作为OS的潜在治疗靶点。
Osteosarcoma (OS) is the most common malignant tumor of bone. It has recently been demonstrated that galectin-3, a multifunctional beta-galactoside-binding, is significantly upregulated in OS tissues, and is correlated with its progression and metastasis. However, the detailed role of galectin-3 in the regulation of cellular biological processes in OS cells has remained to be elucidated. The present study reported that the mRNA and protein levels of galectin-3 were significantly increased in OS tissues compared to those in their matched normal adjacent tissues. Furthermore, galectin-3 was upregulated in three OS cell lines, Saos-2, MG63 and U2OS, when compared with that in the human osteoblast cell line hFOB1.19. Knockdown of galectin-3 by galectin-3-specific small interfering RNA markedly inhibited OS-cell proliferation and induced cell apoptosis. Furthermore, silencing of galectin-3 expression significantly inhibited OS cell migration and invasion, accompanied with a marked decrease in the protein expression of matrix metalloproteinase 2 and -9. Mechanistic investigation suggested that the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase signaling pathway may be involved in the galectin-3-mediated OS cell invasion. In conclusion, the present study was the first to report that silencing of galectin-3 inhibited the malignant phenotypes of osteosarcoma in vitro. Therefore, galectin-3 may serve as a potential therapeutic target for OS.