DEAD-Box Helicase 5 Interacts With Transcription Factor 12 and Promotes the Progression of Osteosarcoma by Stimulating Cell Cycle Progression
Authors: Xin Jiang
Qing Wang
Yongxin Liu
Huancai Liu
Fenghua Zhou
Yawen Zhang
Yanchun Chen
Jinmeng Liu
Qiaozhen Wang
Journal: Frontiers in Pharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cyclin E1; DDX5; MG63 cells; TCF12; osteosarcoma.
Affiliations: Department of Histology and Embryology, School of Clinical Medicine, Weifang Medical University, Weifang, China., Department of Human Anatomy, School of Clinical Medicine, Weifang Medical University, Weifang, China., Department of Anesthesiology, Weifang Medical University, Weifang, China., Department of Pathology, School of Clinical Medicine, Weifang Medical University, Weifang, China., Department of Joint Surgery, Affiliated Hospital, Weifang Medical University, Weifang, China.

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. 

Retracted: Yes

PubPeer comments:
 The  si-DDX5 panel in Figure 2E looks very similar to the  si-DDX5+pENTER-Con panel in Figure 6E. Shown with red boxes. ![file] , 
 2019 retraction. https: www.frontiersin.org articles 10.3389 fphar.2019.01657 full Following publication, concerns were raised regarding the scientific validity of the article. An investigation was therefore conducted in accordance with our established procedures. As the raw data presented in the manuscript could not be provided, the Specialty Chief Editor concluded that the conclusions and assertions could not be sufficiently supported by the material provided. The retraction of the article was approved by the Chief Editors of Pharmacology and the Editor-in-Chief of Frontiers. The authors agree to the retraction. ,