Oncotarget

Research Papers:

Minichromosome maintenance protein 2 and 3 promote osteosarcoma progression via DHX9 and predict poor patient prognosis

Dong-dong Cheng, Hui-zhen Zhang, Jun-qing Yuan, Shi-jie Li, Qing-cheng Yang and Cun-yi Fan _

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Oncotarget. 2017; 8:26380-26393. https://doi.org/10.18632/oncotarget.15474

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Abstract

Dong-dong Cheng1,*, Hui-zhen Zhang2,*, Jun-qing Yuan2,*, Shi-jie Li1, Qing-cheng Yang1, Cun-yi Fan1

1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

2Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

*Authors share co-first authorship

Correspondence to:

Cun-yi Fan, email: fancunyi888@hotmail.com

Qing-cheng Yang, email: tjyqc@163.com

Keywords: MCM2, MCM3, DHX9, proliferation, osteosarcoma

Received: November 14, 2016     Accepted: February 07, 2017     Published: February 18, 2017

ABSTRACT

A label free quantitative proteomic approach (SWATH™ experiment) was performed to identify tumor-associated nuclear proteins that are differentially expressed between osteosarcoma cells and osteoblast cells. By functional screening, minichromosome maintenance protein 2 (MCM2) and minichromosome maintenance protein 3 (MCM3) were found to be related to osteosarcoma cell growth. Here, we show that knockdown of MCM2 or MCM3 inhibits osteosarcoma growth in vitro and in vivo. In co-immunoprecipitation and co-localization experiments, MCM2 and MCM3 were found to interact with DExH-box helicase 9 (DHX9) in osteosarcoma cells. A rescue study showed that the decreased growth of osteosarcoma cells by MCM2 or MCM3 knockdown was reversed by DHX9 overexpression, indicating that MCM2 and MCM3 activity was DHX9-dependent. In addition, the depletion of DHX9 hindered osteosarcoma cell proliferation. Notably, MCM2 and MCM3 expression levels were positively correlated with the DHX9 expression level in tumor samples and were associated with a poor prognosis in patients with osteosarcoma. Taken together, these results suggest that the MCM2/MCM3–DHX9 axis has an important role in osteosarcoma progression.


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