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Updated: Jan 27, 2026
Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma
Published on: October 14, 2016
miR-186-5p Functions as a Tumor Suppressor in Human Osteosarcoma by Targeting FOXK1
Zhiqiang Zhang1, Wen Zhang2, Junsheng Mao1
1Department of Orthopedics, Shandong Provincial Third Hospital, Jinan, China.
Background/Aims:
Aberrantly expressed miRNAs play a vital role in the development of some cancers, such as human osteosarcoma (OS). However, the detailed molecular mechanisms underlying miR-186-5p-involved osteosarcoma are unclear.
Methods:
qRT-PCR and western blot analysis were employed to measure the expressions of miR-186-5p and forkhead box k1 (FOXK1). CCK-8 assay evaluated the effect of miR-186-5p and FOXK1 on cell proliferation. Transwell assay confirmed cell migration and invasion. Eventually, the dual-luciferase reporter assay validated 3'-untranslated region (3'-UTR) of FOXK1 as a direct target of miR-186-5p.
Results:
Down-regulation of miR-186-5p was identified in OS tissues and cell lines, and negatively correlated with distant metastasis, Enneking stage and poor 5-year prognosis as well as the expression of forkhead box k1 (FOXK1) protein. Further assays demonstrated that miR-186-5p overexpression had inhibitory effects on in-vitro cell proliferation, cell cycle, and in-vivo tumor growth. miR-186-5p overexpression also inhibited the epithelial-tomesenchymal transition (EMT), migration and invasion of OS cells. Importantly, miR-186-5p directly targeted FOXK1 3'-UTR and negatively regulated its expression. Silencing of FOXK1 expression enhanced the inhibitory effects of miR-186-5p on OS cell proliferation, migration and invasion.
Conclusion:
These findings highlighted miR-186-5p as a tumor suppressor in the regulation of progression and metastatic potential of OS, and may benefit the development of therapies targeting miR-186-5p in patients with OS.
Insights
MicroRNA-186-5p acts as a tumor suppressor in osteosarcoma (OS) by inhibiting cell proliferation, migration, and invasion. It targets FOXK1, suggesting potential therapeutic strategies for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Aberrant microRNA (miRNA) expression is implicated in cancer development, including human osteosarcoma (OS).
- The specific molecular mechanisms of miR-186-5p in osteosarcoma progression remain incompletely understood.
Purpose of the Study:
- To elucidate the role and molecular mechanisms of miR-186-5p in human osteosarcoma (OS).
- To investigate the relationship between miR-186-5p, forkhead box k1 (FOXK1), and OS progression.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot analysis to assess miR-186-5p and FOXK1 expression.
- Cell Counting Kit-8 (CCK-8) assay for proliferation, Transwell assay for migration and invasion, and dual-luciferase reporter assay to validate target interaction.
- In-vitro and in-vivo experiments to evaluate the functional impact of miR-186-5p and FOXK1.
Main Results:
- Down-regulation of miR-186-5p was observed in OS tissues and cell lines, correlating with metastasis and poor prognosis.
- Overexpression of miR-186-5p suppressed OS cell proliferation, cell cycle progression, epithelial-mesenchymal transition (EMT), migration, and invasion.
- miR-186-5p directly targets the 3'-untranslated region (3'-UTR) of FOXK1, negatively regulating its expression.
Conclusions:
- miR-186-5p functions as a tumor suppressor in osteosarcoma, inhibiting its progression and metastatic potential.
- Targeting miR-186-5p presents a potential therapeutic avenue for osteosarcoma treatment.
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