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MicroRNA-384 downregulates SETD8 expression to suppress cell growth and metastasis in osteosarcoma cells
1Department of Orthopedics, Southern Medical University, Guangzhou, Guangdong, China. zjf3614777@126.com.
Objective:
MiR-384 was reported to be downregulated and functioned as a tumor suppressor in several cancers. However, the expression and function of miR-384 in osteosarcoma (OS) have not been investigated. In the present study, we aimed to analyze the effect and mechanism of miR-384 in the progression of OS.
Patients And Methods:
Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of miR-384 in OS tissues and cells. MTT assay, colony formation analysis, Transwell assays were performed to analyze the role of miR-384 in human OS cells. Western blotting was applied to analyze the expression of SETD8, and the luciferase reporter assay was used to assess the target gene of miR-384 in OS cells.
Results:
We found that miR-384 was significantly lowly expressed in OS tissues and OS cell lines compared with the adjacent noncancerous tissues and normal bone cell lines, respectively. Further functional analysis indicated that up-regulation of miR-384 significantly inhibited OS cells proliferation, migration, and invasion, but down-regulation of miR-384 had the opposite effects on OS cells in vitro. Moreover, SETD8 was identified as the potential target of miR-384 using dual luciferase assay, qRT-PCR and Western blot. Finally, we observed that upregulation of SETD8 reversed the effects of overexpressing of miR-384 on the proliferation, migration, and invasion of OS.
Conclusions:
Our data provided the first evidence which supported the function of miR-384 as a tumor suppressor in OS by targeting SETD8.
Insights
MicroRNA-384 (miR-384) acts as a tumor suppressor in osteosarcoma (OS) by inhibiting cancer cell proliferation, migration, and invasion. It targets SET domain-containing protein 8 (SETD8), and its downregulation is linked to OS progression.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA-384 (miR-384) is a known tumor suppressor in various cancers.
- Its role in osteosarcoma (OS) progression remains unexplored.
Purpose of the Study:
- To investigate the expression and function of miR-384 in osteosarcoma.
- To elucidate the underlying molecular mechanism of miR-384 in OS.
Main Methods:
- Quantitative Real-time PCR (qRT-PCR) for miR-384 expression analysis.
- In vitro assays (MTT, colony formation, Transwell) to assess cell proliferation, migration, and invasion.
- Western blotting and luciferase reporter assays to identify miR-384 targets.
Main Results:
- miR-384 expression was significantly downregulated in OS tissues and cell lines.
- Overexpression of miR-384 inhibited OS cell proliferation, migration, and invasion.
- SET domain-containing protein 8 (SETD8) was identified as a direct target of miR-384.
- SETD8 upregulation reversed the tumor-suppressive effects of miR-384.
Conclusions:
- miR-384 functions as a tumor suppressor in osteosarcoma.
- This effect is mediated through the targeting of SETD8.
- miR-384 represents a potential therapeutic target for osteosarcoma treatment.
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