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

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. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not 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 DJ-1 knockout suppressed 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 a novel therapeutic opportunity for OS patients.

Identification of a novel mitophagy-related signature for predicting clinical prognosis and immunotherapy of osteosarcoma

“…It is also targeted by tiny DNA tumor virus-transforming proteins [30,31] . Han et al revealed that DJ-1 promotes osteosarcoma progression by activating the CDK4/RB/E2F1 signaling pathway [32] . Liu et al found that long noncoding RNA (lncRNA)-TMPO-AS1 promotes osteosarcoma cell apoptosis by targeting and regulating E2F1 [33] .…”

DJ-1: A Potential Biomarker Related to Prognosis, Chemoresistance, and Expression of Microenvironmental Chemokine in HR-Positive Breast Cancer

“…The evidence shows that DJ-1 may be involved in various mechanisms in cancer progression, including the inhibition of cellular apoptosis, redox sensing, acting as a marker for chemotherapy resistance, suppression of ferroptosis, regulating histone glycation, and inhibition of autophagy [9][10][11][12][13]. It has been identified overexpression in a range of cancer types, including breast cancer [14,15], osteosarcoma [16], melanoma [17], colorectal cancer [18], endometrial cancer [19], and esophageal cancer [20], indicating its role as oncogene. Previously, a study in breast cancer cell lines has shown that NRG-I promotes the decoupling of DJ-I with HER3 and activates the heterodimerization of HER2/HER3 [21].…”