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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MiR-323a-3p suppressed the glycolysis of osteosarcoma via targeting LDHA
Hanwen Chen1, Shuming Gao2, Cai Cheng2
1Department of First Orthopedics, Cangzhou Central Hospital, Cangzhou, 061000, Hebei, China. rmyy_med@sina.com.
Abstract:
Accumulating evidence has demonstrated that there is critical involvement of miRNAs in the initiation and progression of cancers. Here, we showed that miR-323a-3p was significantly down-regulated in osteosarcoma (OS) tissues and cell lines. Overexpression of miR-323a-3p decreased the cell viability, colon formation and induced the apoptosis of OS cells. Using bioinformatics analysis, lactate dehydrogenase A (LDHA) was predicted as one of the down-steam targets of miR-323a-3p. Highly expressed miR-323a-3p significantly decreased both the mRNA and protein levels of LDHA. Inverse correlation between the expression of LDHA and miR-323a-3p was observed in OS tissues. Consistent with the function of LDHA in glycolysis of cancer cells, overexpression of miR-323a-3p attenuated the lactate production of OS cells. These results demonstrated that miR-323a-3p suppressed the growth of OS cells via targeting LDHA and inhibited the glycolysis of OS. This study provides insight into the molecular mechanism of miR-323a-3p in regulating OS.
Insights
MicroRNA-323a-3p is down-regulated in osteosarcoma (OS) and suppresses tumor growth by targeting lactate dehydrogenase A (LDHA), inhibiting cancer cell glycolysis.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play a critical role in cancer initiation and progression.
- Dysregulation of specific miRNAs is implicated in various cancers, including osteosarcoma (OS).
Purpose of the Study:
- To investigate the role of miR-323a-3p in osteosarcoma.
- To identify the downstream targets and molecular mechanisms of miR-323a-3p in OS.
Main Methods:
- Quantitative real-time PCR to assess miR-323a-3p and LDHA expression.
- Cell viability, colony formation, and apoptosis assays to evaluate miR-323a-3p function.
- Bioinformatics analysis to predict miR-323a-3p targets.
- Western blot to confirm protein level changes.
- Lactate production assays to assess glycolysis.
Main Results:
- miR-323a-3p was significantly downregulated in OS tissues and cell lines.
- Overexpression of miR-323a-3p inhibited OS cell viability, colony formation, and induced apoptosis.
- Lactate dehydrogenase A (LDHA) was identified as a direct target of miR-323a-3p.
- miR-323a-3p overexpression reduced LDHA mRNA and protein levels.
- An inverse correlation was observed between miR-323a-3p and LDHA expression in OS tissues.
- Overexpression of miR-323a-3p decreased lactate production in OS cells, indicating inhibition of glycolysis.
Conclusions:
- miR-323a-3p acts as a tumor suppressor in osteosarcoma.
- The miR-323a-3p/LDHA axis regulates osteosarcoma cell growth and glycolysis.
- This study elucidates a novel molecular mechanism of miR-323a-3p in OS progression.
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