Minichromosome maintenance protein 2 and 3 promote osteosarcoma progression via DHX9 and predict poor patient prognosis
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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
Cun-yi Fan, email: firstname.lastname@example.org
Qing-cheng Yang, email: email@example.com
Keywords: MCM2, MCM3, DHX9, proliferation, osteosarcoma
Received: November 14, 2016 Accepted: February 07, 2017 Published: February 18, 2017
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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