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Article Open Access

Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway

  • Authors:
    • Zexin Su
    • Bingsheng Yang
    • Zhirui Zeng
    • Shuang Zhu
    • Chenyang Wang
    • Shan Lei
    • Yongfa Jiang
    • Lijun Lin
  • View Affiliations / Copyright

    Affiliations: Department of Joint Surgery, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong 510800, P.R. China, Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Haizhu, Guangzhou, Guangdong 510282, P.R. China, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Department of Physiology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550009, P.R. China, Department of Neurosurgery, Zhujiang Hospital, Neurosurgery Institute of Guangdong Province, Key Laboratory on Brain Function Repair and Rehabilitation, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China
    Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 99-112
    |
    Published online on: April 15, 2020
       https://doi.org/10.3892/ol.2020.11544
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Abstract

Osteosarcoma (OS) is the most common and destructive primary bone malignancy to affect children and adolescents. Metastases remain the primary cause of death in patients with OS. In the present study, weight gene co‑expressed network analysis (WGCNA) and differentially‑expressed gene analysis were used to identify key genes associated with the metastasis of OS. Reverse transcription‑quantitative PCR and immunohistochemical staining were then used to detect the expression levels of these key genes in OS tissues, and to determine the hub genes of interest. Wound‑healing and transwell assays, in addition to a lung metastasis model, were used to detect the effects of the hub genes on OS cell proliferation and metastasis in vitro and in vivo. Using WGCNA and differential expression analysis, deleted in lung and esophageal cancer protein 1 (DLEC1), Forkhead box J1 (FOXJ1) and mitogen‑activated protein kinase 15 (MAPK15) were predicted to be key metastasis‑associated genes, and highly expressed in metastatic OS tissues; among them, the protein and mRNA expression levels of MAPK15 were most significantly increased in our OS tissues from patients who exhibited metastases at diagnosis, and thus MAPK15 was determined to be a metastasis‑associated hub gene to further study. Furthermore, inhibiting MAPK15 expression significantly decreased OS cell metastasis in vitro and in vivo, as well as suppressing c‑Jun/matrix metalloproteinase (MMP)‑associated pathways. Overexpression of MAPK15 activated the c‑Jun/MMPs pathway and promoted OS cell metastasis, while inhibition of c‑Jun blocked this effect. Taken together, MAPK15 was indicated to be an OS metastasis‑associated gene, and was confirmed to promote the migration and invasion of OS cells via the c‑Jun/MMP pathway. MAPK15 may therefore be an effective target for the treatment of OS.
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Copy and paste a formatted citation
Spandidos Publications style
Su Z, Yang B, Zeng Z, Zhu S, Wang C, Lei S, Jiang Y and Lin L: Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway. Oncol Lett 20: 99-112, 2020.
APA
Su, Z., Yang, B., Zeng, Z., Zhu, S., Wang, C., Lei, S. ... Lin, L. (2020). Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway. Oncology Letters, 20, 99-112. https://doi.org/10.3892/ol.2020.11544
MLA
Su, Z., Yang, B., Zeng, Z., Zhu, S., Wang, C., Lei, S., Jiang, Y., Lin, L."Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway". Oncology Letters 20.1 (2020): 99-112.
Chicago
Su, Z., Yang, B., Zeng, Z., Zhu, S., Wang, C., Lei, S., Jiang, Y., Lin, L."Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway". Oncology Letters 20, no. 1 (2020): 99-112. https://doi.org/10.3892/ol.2020.11544
Copy and paste a formatted citation
x
Spandidos Publications style
Su Z, Yang B, Zeng Z, Zhu S, Wang C, Lei S, Jiang Y and Lin L: Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway. Oncol Lett 20: 99-112, 2020.
APA
Su, Z., Yang, B., Zeng, Z., Zhu, S., Wang, C., Lei, S. ... Lin, L. (2020). Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway. Oncology Letters, 20, 99-112. https://doi.org/10.3892/ol.2020.11544
MLA
Su, Z., Yang, B., Zeng, Z., Zhu, S., Wang, C., Lei, S., Jiang, Y., Lin, L."Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway". Oncology Letters 20.1 (2020): 99-112.
Chicago
Su, Z., Yang, B., Zeng, Z., Zhu, S., Wang, C., Lei, S., Jiang, Y., Lin, L."Metastasis‑associated gene MAPK15 promotes the migration and invasion of osteosarcoma cells via the c‑Jun/MMPs pathway". Oncology Letters 20, no. 1 (2020): 99-112. https://doi.org/10.3892/ol.2020.11544
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