AUTHOR=Han Zhitao , Wang Lining , Wang Dongshuo , Zhang Luosheng , Bi Yifeng , Zheng Xinlei , Liu Weibo , Bai Guangjian , Wang Zhenhua , Wan Wei , Ma Yong , Cai Xiaopan , Liu Tielong , Jia Qi 

TITLE=DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1036401

DOI=10.3389/fonc.2022.1036401

ISSN=2234-943X

ABSTRACT=Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. In this study, we found that DJ-1 was upregulated in OS and the level of DJ-1 was closely correlated with the prognosis of patients, and that DJ-1 could promote the proliferation, migration and chemotherapy-resistant of OS cells in vitro through regulating the activity of CDK4 rather through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that knockout of DJ-1 suppresses tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting novel therapeutic opportunities for OS patients.