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Published on: October 28, 2021
miR-24 represses metastasis of human osteosarcoma cells by targeting Ack1 via AKT/MMPs pathway
Zhendong Liu1, Zhitao Liu1, Yuanjun Zhang1
1Department of Orthopedic Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Abstract:
The expression levels of the protein tyrosine kinase Ack1 has been reported to be dysregulated in various cancers and involve in oncogenesis and progression. However, the expression and role of Ack1 in osteosarcoma remains unknown. In this study, we found that Ack1 were evidently upregulated in human osteosarcoma tissues and cell lines. In addition, the clinical data showed that high expression level of Ack1 is closely associated with clinical stage and positive distant metastasis, and negatively correlated with overall survival. Then, bioinformatics prediction and luciferase reporter assay indicated Ack1 as a direct target of miR-24, and Ack1 could be downregulated by miR-24 at both the mRNA and protein expression levels. Moreover, Ack1 expression levels were inversely correlated with that of miR-24 in osteosarcoma tissues. Furthermore, functional assay showed that miR-24 significantly suppressed osteosarcoma progression partially mediated by inhibiting Ack1 expression. Finally, western bolt assay revealed that miR-24 regulate AKT/MMPs pathway via Ack1 in osteosarcoma cells. In conclusion, our study demonstrated the suppression of miR-24 on osteosarcoma metastasis by targeting Ack1 via AKT/MMPs pathways, providing a novel strategy for the diagnosis and treatment of osteosarcoma patients.
Insights
MicroRNA-24 (miR-24) suppresses osteosarcoma progression by targeting Ack1 (a protein tyrosine kinase). This inhibition impacts the AKT/MMPs pathway, offering a potential new strategy for osteosarcoma diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Protein tyrosine kinase Ack1 is dysregulated in various cancers, but its role in osteosarcoma is unknown.
- Ack1 is implicated in oncogenesis and cancer progression.
- Understanding Ack1's role in osteosarcoma is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression and role of Ack1 in human osteosarcoma.
- To determine the relationship between Ack1 and microRNA-24 (miR-24) in osteosarcoma.
- To elucidate the underlying molecular mechanisms of miR-24's function in osteosarcoma progression.
Main Methods:
- Quantitative analysis of Ack1 expression in osteosarcoma tissues and cell lines.
- Bioinformatics prediction and luciferase reporter assays to confirm miR-24 targeting of Ack1.
- Functional assays to assess the impact of miR-24 on osteosarcoma cell progression.
- Western blot analysis to investigate the role of Ack1 in the AKT/MMPs pathway.
Main Results:
- Ack1 expression is significantly upregulated in osteosarcoma and correlates with advanced clinical stage, metastasis, and poor survival.
- Ack1 is a direct target of miR-24, with miR-24 downregulating Ack1 expression.
- miR-24 suppresses osteosarcoma progression by inhibiting Ack1, partially via the AKT/MMPs pathway.
Conclusions:
- miR-24 acts as a tumor suppressor in osteosarcoma by targeting Ack1.
- The miR-24/Ack1 axis regulates the AKT/MMPs pathway, influencing osteosarcoma metastasis.
- Targeting the miR-24/Ack1 interaction presents a novel therapeutic strategy for osteosarcoma.
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