Abstract
Osteosarcoma (OS) is a common malignant primary bone tumor. Its mechanism of development and progression is poorly understood. Currently, there is no effective therapeutic regimens available for the treatment of OS. DEAD-box helicase 5 (DDX5) is involved in oncogenic processes. This study aimed to explore the role of DDX5 in the development and progression of OS and its relationship with transcription factor 12 (TCF12), which is as an important molecule of Wnt signaling pathway. We found that the expressions of DDX5 and TCF12 protein were significantly higher in OS patients tissues and in the MG63 cells than in the corresponding normal tissues and human osteoblast cell hFOB 1.19. Overexpressions of both DDX5 and TCF12 were associated with clinicopathological features and poor prognosis of OS patients. siRNA based knockdown of DDX5 inhibited the proliferation of MG63 cells as demonstrated by an in vitro MTS assay and 5-ethynyl-2-deoxyuridine DNA proliferation detection, and promoted apoptosis of MG63 cells measured by flow cytometry. In addition, DDX5 knockdown inhibited the MG63 cell migration and invasion on transwell assays. Further experiments showed that DDX5 knockdown not only inhibited the expression of TCF12 but also decreased the mRNA and protein levels of Cyclin E1, an important regulator of G1–S phase progression, suggesting that DDX5 was required for the entry of cells into S phase. Overexpression of TCF12 reversed the cell proliferation, migration and invasion in MG63 cells induced by DDX5 knockdown accompanied by the upregulation of Cyclin E1. Additionally, we observed that DDX5 interacted with TCF12 in both OS tissues and MG63 cells by Co-immunoprecipitation assays. Taken together, our study revealed that DDX5 interacts with TCF12 and promotes the progression of OS by stimulating cell cycle progression. Our results suggest that DDX5 and TCF12 could be potential biomarkers for the diagnosis and treatment of OS.
Highlights
MATERIALS AND METHODSOsteosarcoma (OS) is a highly malignant primary bone tumor Patient Information and Tissue Samples in children and adolescence
Western blot analysis of MG63 and hFOB 1.19 cells showed that DEAD-box helicase 5 (DDX5) and transcription factor 12 (TCF12) were upregulated in MG63 cells compared with hFOB 1.19 cells (P < 0.01) (Figures 1B,C), suggesting that DDX5 and TCF12 were overexpressed in both human OS samples and OS MG63 cells
Spearman’s correlation analysis revealed that the expressions of DDX5 and TCF12 showed a positive correlation (r = 0.491, P < 0.01). These results indicate that DDX5 and TCF12 were overexpressed in highly proliferative OS tissues and cells, and could be important prognostic biomarkers of OS
Summary
Osteosarcoma (OS) is a highly malignant primary bone tumor Patient Information and Tissue Samples in children and adolescence. It is characterized by pathologic bone destruction and early lung metastasis (Mirabello et al, 2009; Gill et al, 2013). There are some therapies available, including surgical resection and chemotherapy, its survival rate remains low (Saraf et al, 2018), indicating the ineffectiveness of current therapy. A total of 72 formalin-fixed and paraffin-embedded OS specimens and the paired adjacent normal tissues were derived from the Affiliated Hospital and the People’s Hospital of Weifang Medical University from 2001 to 2010. Overall survival rate of all patients was calculated from the diagnosis date to the date of death.
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