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Updated: Dec 8, 2025

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
MicroRNA-615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2
Limin Sun1, Peng Wang1, Zhiqiang Zhang1
1Department of Orthopedics, Shandong Provincial Third Hospital, Jinan, Shandong 250031, P.R. China.
Abstract:
At present, the regulatory mechanisms of various microRNAs (miRNAs/miRs) have been elucidated in human cancers including osteosarcoma (OS). This study mainly focused on the role of miR-615 in OS, which has not yet been reported. Ninety-two OS tissues and normal samples were used in this study. Human osteoblast hFOB1.19 cells and OS cell line HOS were utilized to detect the expression of miR-615. The expression of miR-615 and gene expression were assessed by RT-qPCR and western blot analysis. Transwell, MTT and luciferase reporter assays were used to investigate the regulatory mechanism of miR-615 in OS. The results revealed that miR-615 expression was reduced in OS tissues and cells, and was associated with poor clinical outcomes and prognosis in OS patients. In addition, overexpression of miR-615 restrained cell viability and metastasis in OS. Furthermore, hexokinase 2 (HK2) was confirmed as a direct target of miR-615. Upregulation of HK2 was detected in OS tissues. The upregulation of HK2 weakened the tumor-suppressive effect of miR-615 in OS. Moreover, miR-615 blocked epithelial-mesenchymal transition (EMT) and inactivated the PI3K/AKT pathway in OS. To conclude, miR-615 acts as a tumor suppressor in OS, thus miR-615 can be used as a target for OS treatment.
Insights
MicroRNA-615 (miR-615) functions as a tumor suppressor in osteosarcoma (OS). Reduced miR-615 expression correlates with poor prognosis, and its restoration inhibits OS progression by targeting hexokinase 2 (HK2).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are crucial regulators in human cancers, including osteosarcoma (OS).
- The specific role of miR-615 in osteosarcoma pathogenesis remained largely uninvestigated.
- Understanding miRNA roles is vital for developing novel cancer therapies.
Purpose of the Study:
- To investigate the expression and function of miR-615 in human osteosarcoma.
- To elucidate the regulatory mechanism of miR-615 in OS progression.
- To evaluate miR-615 as a potential therapeutic target for osteosarcoma.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blot analysis for gene expression.
- Cellular assays including Transwell and MTT for proliferation and metastasis.
- Luciferase reporter assays to confirm direct gene targets.
Main Results:
- miR-615 expression was significantly downregulated in OS tissues and cell lines.
- Lower miR-615 levels correlated with adverse clinical outcomes and poor prognosis in OS patients.
- Overexpression of miR-615 suppressed OS cell viability and metastasis, identifying HK2 as a direct target.
- miR-615 inhibited epithelial-mesenchymal transition (EMT) and inactivated the PI3K/AKT pathway.
Conclusions:
- miR-615 acts as a tumor suppressor in osteosarcoma.
- Restoring miR-615 levels may offer a novel therapeutic strategy for OS.
- The miR-615/HK2 axis plays a critical role in OS development and progression.
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