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Silencing of carboxypeptidase E inhibits cell proliferation, tumorigenicity, and metastasis of osteosarcoma cells

Authors Fan S, Li X, Li L, Wang L, Du Z, Yang Y, Zhao J, Li Y

Received 23 October 2015

Accepted for publication 13 February 2016

Published 10 May 2016 Volume 2016:9 Pages 2795—2803


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 6

Editor who approved publication: Dr Faris Farassati

Shuli Fan,1,* Xu Li,2,* Leiming Li,2 Liguo Wang,2 Zhangzhen Du,2 Yan Yang,2 Jiansong Zhao,3 Yan Li3

1Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China

*These authors contributed equally to this work

Abstract: Carboxypeptidase E (CPE), a prohormone processing enzyme, has been implicated in the progression of multiple malignancies. However, the biological role and molecular mechanisms of CPE in osteosarcoma remain elusive. In this study, we assessed the effects of CPE on cell proliferation, tumorigenicity, migration, and invasion in osteosarcoma. Our results showed that silencing of CPE significantly inhibited cell proliferation, caused cell cycle arrest at G0/G1 phase, decreased the expression levels of cell cycle protein, cyclin D1, and inhibited tumorigenicity in vivo. Additionally, CPE downregulation repressed the migratory and invasive capacities of osteosarcoma cells in vitro. Furthermore, overexpression of CPE-ΔN (a splice variant of CPE) enhanced the cell growth, migration, and invasion of osteosarcoma cells. It is possible that both CPE forms are involved in the tumorigenesis and development of osteosarcoma, and therefore CPE may provide a promising biological target for osteosarcoma therapy.

Keywords: carboxypeptidase E, osteosarcoma, proliferation, tumorigenicity, migration, invasion

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