The Mechanism Of Interaction Between PELI1 And PLK1 In The Progression Of Osteosarcoma

Objective: Numerous studies have found that PELI1 plays an important role in the process of tumor genesis and development,which involves the crossover and activation of multiple pathways.However,the mechanism of PELI1 in osteosarcoma remains unclear.The main purpose of this study is to explore the specific role and regulatory mechanism of PELI1 in the progression of osteosarcoma,provide new ideas for the diagnosis and treatment of osteosarcoma,and finally apply it to clinical practice.Methods: Firstly,the expression of PELI1 in osteosarcoma tissues and paracancer tissues was detected by immunohistochemistry.Then,real-time quantitative PCR was used to detect the expression level of PELI1 in different osteosarcoma cell lines,and four osteosarcoma cell lines(143B(gene knockdown),U2R(overexpression),U2 OS and MG63)were selected for PELI1 function experiments.We knocked down or overexpressed PELI1 in different osteosarcoma cell lines,and investigated the role of PELI1 in the proliferation and migration of osteosarcoma cells through a series of cell function experiments,including MTT assay,Wound Healing assay,Transwell assay,Clone formation assay and flow cytometry for cell cycle and apoptosis.Then,GEPIA database was used to analyze the expression of PELI1 in sarcoma tissues,and a tandem affinity purification and mass spectrometry(TAP-MS)assay were performed on PELI1 to screen out genes interacting with PELI1,their interactions were further determined by co-immunoprecipitation in vitro.293 T cells were used to explore the effects and regulation of PELI1 and the screened genes(PLK1)on their protein expression levels.After elucidating the regulatory mechanism in 293 T cells,the endogenous changes of each protein were detected by osteosarcoma cell lines,so as to study the post-translational regulatory mechanism of PELI1.Results: In this study,we found that the expression of PELI1 in osteosarcoma tissues was significantly lower than that in paracancer tissues.High expression of PELI1 inhibited the proliferation and migration of osteosarcoma cells and promoted the occurrence of apoptosis.Knockdown of PELI1 had the opposite effect in osteosarcoma cells.Moreover,through the TAP-MS results,PLK1 was screened out and its interaction with PELI1 was verified.PLK1 significantly regulated endogenous and exogenous PELI1,and high expression of PLK1 decreased PELI1 protein level.In terms of the mechanism,we confirmed that PELI1 can affect the proliferation,metastasis and apoptosis of osteosarcoma cells,and its expression is regulated by PLK1.PELI1 expression is negatively correlated with PLK1.PELI1 can interact with PLK1 to play a pivotal role in the progression of osteosarcoma.Conclusions: PELI1 can inhibit the proliferation and metastasis of osteosarcoma cells and induce apoptosis,and its expression is regulated by PLK1 in this process.This finding may provide a new strategy for the clinical treatment of osteosarcoma and improve the prognosis of patients.