Interfering with pak4 Protein Expression Affects Osteosarcoma Cell Proliferation and Migration.

Yuxin Fu,Lun Fang,Lu Zhou,Qi Wu,Qipu Yin,Xindi Zhao,Ying Sun,Yadi Wu,Wei Sui

doi:10.1155/2021/9977001

Abstract

Purpose 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. Materials and Methods 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. Results 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. Conclusion Interfering with PAK4 protein expression has been shown to affect osteosarcoma proliferation and migration.

Highlights

Osteosarcoma (OS), a primary malignant bone tumor, is characterized by triangular stromal cells originating from primitive intercellular cells and producing osteoid tissue [1]
For ensuring the expression of PAK4 in OS, we detected the expression of PAK4 in OS cell lines; as Figure 1(a) shows, PAK4 was lower in OS cell lines U2-OS and MG-63 than in osteoblastic cell hFOB
These findings suggested that PAK4 dysregulation could be a predictor of OS prognosis

Summary

Introduction

Osteosarcoma (OS), a primary malignant bone tumor, is characterized by triangular stromal cells originating from primitive intercellular cells and producing osteoid tissue [1]. It is most commonly seen in the adolescent metaphysis of the long bones of the extremities [2]. Amputation was the only treatment option for osteosarcoma patients in the 1970s, with less than 20% of a 5-year survival rate. Osteosarcoma has a high risk of lung metastasis, and patients suffering from lung metastasis showed poor prognosis, with a 20% of 5-year survival rate [4]. The discovery of new biomarkers linked to progression, and prognosis may improve the treatment and prognosis for patients with osteosarcoma

Methods

Results

Discussion

Conclusion