Down regulation of human positive coactivator 4 suppress tumorigenesis and lung metastasis of osteosarcoma
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Xu Hu1,*, Chao Zhang1,*, Ying Zhang1, Christopher S. Hong3, Wugui Chen1, Weiwei Shen1, Hongkai Wang1, Jianrong He1, Pei Chen1, Yue Zhou1, Chunmeng Shi2,** and Tongwei Chu1,**
1Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China
2Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China
3The Ohio State University, College of Medicine, Columbus, OH, 43210, USA
*These authors contributed equally to this work
**These authors jointly directed this work
Chunmeng Shi, email: firstname.lastname@example.org
Tongwei Chu, email: Chtw@sina.com
Keywords: PC4, SP1, MMP, pulmonary metastasis
Received: March 01, 2017 Accepted: May 10, 2017 Published: May 30, 2017
Osteosarcoma is a kind of primary malignant bone tumor with the highest incidence and an extraordinarily poor prognosis and early pulmonary metastasis formation as a frequent occurrence. Transcriptional positive coactivator 4 (PC4) has multiple functions in DNA replication, transcription, repair and chromatin organization, even in tumorigenesis. However, the precise function of PC4 in osteosarcoma is still unclear and controversial. In this paper we found PC4 was upregulated in patient-derived osteosarcoma tissues compared to normal. Moreover, higher expression of PC4 was correlated with poorer overall survival and advanced clinicopathological tumor staging. Down regulation of PC4 in the highly metastatic osteosarcoma cells reduced the malignant behaviors in vitro and in vivo. Analyzing the downstream genes affected obviously by shPC4 with RNA sequencing, we found knocking down PC4 will inhibit the propensity for lung metastasis through transcriptional suppression of MMPs pathways. Taken together, PC4 may be an attractive therapeutic strategy for osteosarcoma, especially in preventing lung metastasis formation.
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