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Osteosarcoma is one of the most common malignant bone tumors. The mechanisms of osteosarcoma development and invasion have been studied for periods of time, yet targeted therapy for improving survival has not been well established. Histone lysine methyltransferase NSD2 was frequently overexpressed in multiple types of cancer such as multiple myeloma, stomach and colon cancer, and the overexpression of it usually associated with aggressiveness tumor type. However, the expression status and function of NSD2 are still ambiguous in osteosarcoma. Here, we evaluate the abnormal expression levels of NSD2 in osteosarcoma samples and cell lines. The higher expression of NSD2 in tumors resulted in a poorer outcome and a worse 5-year overall survival. To investigate the role of NSD2 in osteosarcoma cell proliferation and invasion in vitro, MTT assay, cell cycle distribution, wound healing, transwell assay was performed in relative cell lines, using a recombinant lentivirus expressing NSD2 short hairpin RNA or NSD2 construction. Our results imply that NSD2 promotes osteosarcoma cell proliferation and invasion, and the mechanism was possibly through the suppression of E-cadherin and induction of the epithelial mesenchymal transition, further to proceed invasion of osteosarcoma cells.  NSD2 may work as a novel repression of E-cadherin; therefore, NSD2 has potential as a target of OS therapy. In the future, the monitoring of NSD2 in the serum/plasma from the RNA level may be used as a non-invasive method for selecting patients for target therapy.

Citation

M-H Lu, M-F Fan, X-D Yu. NSD2 promotes osteosarcoma cell proliferation and metastasis by inhibiting E-cadherin expression. European review for medical and pharmacological sciences. 2017 Mar;21(5):928-936

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PMID: 28338204

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