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Updated: Feb 8, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MicroRNA-645 promotes metastasis of osteosarcoma via targeting tumor suppressor NM23 nucleoside diphosphate kinase 2
Guang-Jun Jiao1, Shi-Jun Zhang1, Yi Li1
1Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.
Abstract:
Osteosarcoma is the most common non-hematological primary bony malignancy in children and young adults with tumor metastasis being a common event at diagnosis. Understanding the pathogenesis of metastatic osteosarcoma may help identify potential therapeutic targets. In this study, we found that the level of microRNA-645 (miR-645) in osteosarcoma tumor tissues was significantly increased compared with their paired non-tumorous tissues, and was associated with histologic grade, TNM staging, lymph metastasis and distant metastasis. Knockdown of miR-645 caused a remarkable inhibition of migration of osteosarcoma U2OS cells. Furthermore, miR-645 inhibited NME2 (nucleoside diphosphate kinase 2) expression through directly binding to its 3' untranslated region. In human osteosarcoma tissues, we also found that NME2 was significantly decreased in tumor tissues, and its level was negatively correlated with miR-645. In addition, silencing NME2 attenuated the decreased cell migration by knockdown of miR-645, suggesting that it was involved in the miR-645 induced cell migration of osteosarcoma cells. Taken together, we found that miR-645 was up-regulated in osteosarcoma tissues and could promote osteosarcoma cell migration through directly inhibiting the tumor suppressor NME2. Our data provide novel insight into the role of miR-645 in osteosarcoma and indicate that miR-645 might be a potential therapeutic target of osteosarcoma.
Insights
MicroRNA-645 (miR-645) promotes osteosarcoma cell migration by inhibiting the tumor suppressor NME2. This finding highlights miR-645 as a potential therapeutic target for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma is a prevalent bone cancer in young individuals, frequently presenting with metastasis.
- Understanding the molecular mechanisms driving osteosarcoma metastasis is crucial for identifying new therapeutic strategies.
Purpose of the Study:
- To investigate the role of microRNA-645 (miR-645) in osteosarcoma pathogenesis and metastasis.
- To identify the molecular targets of miR-645 involved in osteosarcoma cell migration.
Main Methods:
- Quantitative analysis of miR-645 and NME2 expression in osteosarcoma tissues.
- In vitro experiments involving miR-645 knockdown and NME2 silencing in osteosarcoma cells (U2OS).
- Cell migration assays and analysis of miR-645 binding to the NME2 3' untranslated region.
Main Results:
- miR-645 levels were significantly elevated in osteosarcoma tissues and correlated with advanced disease features.
- Knockdown of miR-645 inhibited osteosarcoma cell migration.
- miR-645 directly suppressed NME2 expression, and NME2 levels were inversely correlated with miR-645 in patient tissues.
- Silencing NME2 partially reversed the effect of miR-645 knockdown on cell migration.
Conclusions:
- miR-645 is upregulated in osteosarcoma and promotes tumor cell migration by inhibiting the tumor suppressor NME2.
- The miR-645/NME2 pathway represents a novel mechanism in osteosarcoma metastasis.
- miR-645 emerges as a potential therapeutic target for managing osteosarcoma metastasis.
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