Oncotarget

Research Papers:

FKBP14 overexpression contributes to osteosarcoma carcinogenesis and indicates poor survival outcome

Zhongming Huang, Junhua Li, Shaohua Du, Yanghua Tang, Ligang Huang, Luwei Xiao and Peijian Tong _

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Oncotarget. 2016; 7:39872-39884. https://doi.org/10.18632/oncotarget.9524

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Abstract

Zhongming Huang1,2,3,4, Junhua Li1,2, Shaohua Du5, Yanghua Tang1,2, Ligang Huang3, Luwei Xiao3,4,6, Peijian Tong3,4,6

1Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China

2Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China

3Zhejiang Chinese Medical University, Hangzhou 310053, China

4Institute of Orthopaedics and Traumatology of Zhejiang Province, Hangzhou 310053, China

5Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310053, China

6Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China

Correspondence to:

Zhongming Huang, email: doctorhzm@gmail.com

Peijian Tong, email: t_peijian@163.com

Keywords: osteosarcoma, FKBP14, GSEA, proliferation, apoptosis

Received: October 27, 2015     Accepted: April 16, 2016     Published: May 20, 2016

ABSTRACT

The FK506-binding protein 14 (FKBP14) is a subfamily of immunophilins, has been implicated in various biochemical processes. However, its effects on the primary malignant bone tumor, osteosarcoma, are unclear. Here, we reported that FKBP14 may be an oncogene as it overexpressed in osteosarcoma tissues and cell lines, and FKBP14 expression was correlated with metastases, recurrence, tumor maximum diameter and poor survival time. FKBP14 was associated with the biological pathways including cell cycle, apoptosis and metastasis. Furthermore, we detected FKBP14 knockdown induced cell cycle arrest, apoptosis, invasion and adhesion in vitro. FKBP14 knockdown decreased the protein levels of PCNA, CDK1 and CCNB1 that promotes cell cycle, increased Bax, caspase-3 and caspase-7 protein involved in promoting cell apoptosis, and increased KIF4A expression as well as decreased SMC4 and TMEM33 proteins that contribute to cell invasion and adhesion. In addition, FKBP14 knockdown also caused a significant inhibition in tumor growth in vivo. Then, we found that the protein RhoA was identified as a binding partner of FKBP14. Taken together, FKBP14 may act as an oncogene in osteosarcoma via suppressing apoptosis and promoting invasion and adhesion in osteosarcoma carcinogenesis. FKBP14 may be a prognostic factor and potential target for osteosarcoma treatment.


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