Department of Orthopedics, Shandong Provincial Western Hospital, Jinan.
Department of Orthopedics, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng.
Anticancer Drugs. 2020 Apr;31(4):326-332. doi: 10.1097/CAD.0000000000000851.
Leucine proline-enriched proteoglycan 1 has been extensively explored because of its protective function in cell homeostasis and correlation with osteogenesis imperfect. Human osteosarcoma is the most common primary malignant tumor of bone with multiple and complex genomic aberrations. However, the functional role of leucine proline-enriched proteoglycan 1 is still unknown in osteosarcoma. Thus we performed this study to explain the leucine proline-enriched proteoglycan 1 effect in osteosarcoma. Gene arrays of human osteosarcoma were downloaded from the Gene Expression Omnibus database. Quantitative real-time PCR was conducted to assess the expression of leucine proline-enriched proteoglycan 1 in osteosarcoma cell lines. Then we attenuated leucine proline-enriched proteoglycan 1 expression in MG63 cells by siRNA strategy and assessed the effect of leucine proline-enriched proteoglycan 1 on cell proliferation, migration and invasion through in-vitro experiments. Additionally, we detected the role of leucine proline-enriched proteoglycan 1 knockdown on PI3K/AKT pathway-related proteins using western blotting. Leucine proline-enriched proteoglycan 1 was increased in osteosarcoma tissues and cells. The overall survival curve demonstrated that high-regulated leucine proline-enriched proteoglycan 1 was linked with poor prognosis of patients with osteosarcoma. The capabilities of proliferation, migration and invasion were all inhibited in MG63 cell because of the downregulation of leucine proline-enriched proteoglycan 1. Furthermore, the expression of phosphorylated PI3K and AKT was impaired after knockdown the leucine proline-enriched proteoglycan 1 as well as P70S6K. In conclusion, leucine proline-enriched proteoglycan 1 might function as an important therapeutic factor in human osteosarcoma through regulating the PI3K/AKT signaling pathway.
富含亮氨酸的脯氨酸聚糖蛋白 1 因其在细胞内稳态中的保护功能以及与成骨不全的相关性而被广泛研究。人类骨肉瘤是最常见的原发性骨恶性肿瘤，具有多种复杂的基因组异常。然而，富含亮氨酸的脯氨酸聚糖蛋白 1 在骨肉瘤中的功能作用尚不清楚。因此，我们进行了这项研究，以解释富含亮氨酸的脯氨酸聚糖蛋白 1 在骨肉瘤中的作用。从基因表达综合数据库中下载了人类骨肉瘤的基因芯片。通过定量实时 PCR 评估富含亮氨酸的脯氨酸聚糖蛋白 1 在骨肉瘤细胞系中的表达。然后，我们通过 siRNA 策略减弱 MG63 细胞中富含亮氨酸的脯氨酸聚糖蛋白 1 的表达，并通过体外实验评估富含亮氨酸的脯氨酸聚糖蛋白 1 对细胞增殖、迁移和侵袭的影响。此外，我们使用 Western blot 检测了富含亮氨酸的脯氨酸聚糖蛋白 1 敲低对 PI3K/AKT 通路相关蛋白的作用。富含亮氨酸的脯氨酸聚糖蛋白 1 在骨肉瘤组织和细胞中上调。总体生存曲线表明，高调节的富含亮氨酸的脯氨酸聚糖蛋白 1与骨肉瘤患者的预后不良相关。由于富含亮氨酸的脯氨酸聚糖蛋白 1 的下调，MG63 细胞的增殖、迁移和侵袭能力均受到抑制。此外，富含亮氨酸的脯氨酸聚糖蛋白 1 敲低后，磷酸化 PI3K 和 AKT 的表达也受到损害，以及 P70S6K。总之，富含亮氨酸的脯氨酸聚糖蛋白 1 可能通过调节 PI3K/AKT 信号通路在人类骨肉瘤中作为一种重要的治疗因子发挥作用。
