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Published on: February 22, 2015
MiR-513c suppresses neuroblastoma cell migration, invasion, and proliferation through direct targeting glutaminase
Hong-Liang Xia1,1, Yao Lv2,1, Chun-Wei Xu3
1Department of Surgery, Children's Hospital of Soochow University, Soochow University, Suzhou, Jiangsu 215000, China.
Abstract:
Neuroblastoma is a malignancy [corrected] of childhood and accounts for 7-10% of childhood cancers, leading to approximately 15% of pediatric cancer deaths. MicroRNAs (miRNAs) are a family of short (about 18-25 nucleotides), noncoding and single stranded endogenous RNAs, which complementarily bind to the 3' untranslated regions of their target genes. Recently, glutamine metabolism has been recognized as an important nutrition source for tumor cells, and hence targeting glutamine metabolism could benefit to development of anti-cancer agents. In this study, we investigate the roles of miR-513c in human neuroblastoma. We report miR-513c is significantly downregulated in human neuroblastoma tissues compared with their adjacent normal tissues. Moreover, miR-513c is significantly downregulated in neuroblastoma cell lines compared with normal neuroblast cells. Overexpression of miR-513c suppresses neuroblastoma cells' migration, invasion, and proliferation. We demonstrate the glutaminase (GLS) is a direct target of miR-513c in human neuroblastoma cells. In addition, we found restoration of GLS expression recovered the neuroblastoma cells' migration, invasion, and proliferation. In summary, this study illustrates a miR-513c mediated neuroblastoma cells suppression, providing a new aspect on the miRNA-based therapeutic approach for the treatments of neuroblastoma.
Insights
MicroRNAs (miRNAs), specifically miR-513c, are downregulated in neuroblastoma. Restoring miR-513c levels suppresses tumor growth by targeting glutaminase (GLS), offering a potential miRNA-based therapy for this childhood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neuroblastoma is a significant pediatric cancer, accounting for 7-10% of childhood cancers and 15% of pediatric cancer deaths.
- MicroRNAs (miRNAs) are short, noncoding RNAs regulating gene expression, and glutamine metabolism is crucial for tumor cell survival.
- Targeting glutamine metabolism presents a promising strategy for developing novel anti-cancer agents.
Purpose of the Study:
- To investigate the role of miR-513c in human neuroblastoma.
- To determine if miR-513c can suppress neuroblastoma progression.
- To identify the molecular targets of miR-513c in neuroblastoma.
Main Methods:
- Comparative analysis of miR-513c expression in neuroblastoma tissues and cell lines versus normal controls.
- Functional assays to assess the impact of miR-513c overexpression on neuroblastoma cell migration, invasion, and proliferation.
- Luciferase reporter assays and Western blotting to validate glutaminase (GLS) as a direct target of miR-513c.
Main Results:
- miR-513c was significantly downregulated in human neuroblastoma tissues and cell lines.
- Overexpression of miR-513c inhibited neuroblastoma cell migration, invasion, and proliferation.
- Glutaminase (GLS) was identified as a direct target of miR-513c, and its restoration reversed the suppressive effects of miR-513c.
Conclusions:
- miR-513c plays a tumor-suppressive role in human neuroblastoma.
- The miR-513c/GLS axis is a critical regulator of neuroblastoma cell behavior.
- miR-513c represents a potential therapeutic target for neuroblastoma treatment.
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