Institute of Sports Medicine, Shandong First Medical University & Shandong Academy Medical Sciences, 619 Changcheng Road, Taian, 271016 Shandong, China.
Taian Maternal and Child Health Hospital, 386 Longtan Road, Taian, 271000 Shandong, China.
Biomed Res Int. 2021 Dec 30;2021:9977001. doi: 10.1155/2021/9977001. eCollection 2021.
A number of studies have discovered various roles of PAK4 in human tumors, including osteosarcoma. However, the exact role of PAK4 in osteosarcoma and its mechanism have yet to be determined. Therefore, this study focused on interrogating the PAK4 effect on the proliferation and migration ability of osteosarcoma and its underlying mechanisms.
Western blot and QRT-PCR were utilized to quantify the PAK4 relative protein and mRNA levels. To measure cellular viability and mobility, the MTT and wound-healing assays were preferred.
With the adenovirus-mediated overexpression of PAK4, the proliferation and migration of U2-OS and MG-63 osteosarcoma cells were stimulated. Furthermore, a liposome-mediated knockout of PAK4 will inhibit osteosarcoma cells from proliferating. In terms of mechanism, we observed the positive correlation of PAK4 expression with expression of P21, CyclinD1, CyclinE1, CDK2, and CDK6, which drives G0/G1 to the G2/M phase transition. PAK4 can also activate Erk expression in OS cells and induce EMT.
Interfering with PAK4 protein expression has been shown to affect osteosarcoma proliferation and migration.
多项研究发现 PAK4 在人类肿瘤中具有多种作用,包括骨肉瘤。然而,PAK4 在骨肉瘤中的确切作用及其机制尚待确定。因此,本研究重点探讨了 PAK4 对骨肉瘤增殖和迁移能力的影响及其潜在机制。
采用 Western blot 和 QRT-PCR 定量检测 PAK4 相对蛋白和 mRNA 水平。采用 MTT 和划痕愈合实验检测细胞活力和迁移能力。
通过腺病毒介导的 PAK4 过表达,可刺激 U2-OS 和 MG-63 骨肉瘤细胞的增殖和迁移。此外,脂质体介导的 PAK4 敲除可抑制骨肉瘤细胞的增殖。在机制方面,我们观察到 PAK4 表达与 P21、CyclinD1、CyclinE1、CDK2 和 CDK6 的表达呈正相关,这导致 G0/G1 向 G2/M 期过渡。PAK4 还可以激活 OS 细胞中的 Erk 表达,并诱导 EMT。
干扰 PAK4 蛋白表达会影响骨肉瘤的增殖和迁移。