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Updated: Sep 27, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
KLF9 regulates miR-338-3p/NRCAM axis to block the progression of osteosarcoma cells
Yunlu Liu1, Kuijing Han2, Yulin Cao1
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
Background: MiR-338-3p is revealed to serve as a tumor suppressor in several carcinomas. Whereas, the effect of miR-338-3p in the progression of osteosarcoma has not been explored. The aim of this paper was to analyze the functional influences of miR-338-3p on osteosarcoma progression and the potential mechanism. Methods: The expression of genes and miRNAs in osteosarcoma cells was assessed via western blotting or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Osteosarcoma cellular proliferation was explored by MTT and EdU incorporation assay. Osteosarcoma cellular migratory and invasive capacity was explored by wound-healing and transwell assay. Bioinformatics approaches were adopted to predict target genes. The relationships between miR-338-3p and neuron‑glial‑related cell adhesion (NRCAM), between kruppel-like factor 9 (KLF9) and miR-338-3p were verified by dual-luciferase reporter assay. Results: We found that miR-338-3p was reduced in osteosarcoma and that higher expression of miR-338-3p suppressed proliferative, invasive and migratory ability of osteosarcoma cells. Furthermore, the result showed that overexpression of NRCAM could reduce the anti-tumor role of miR-338-3p in osteosarcoma cells. In addition, we found that overexpression of KLF9 could enhance the expression level of miR-338-3p in osteosarcoma cells. Conclusion: The KLF9/miR-338-3p/NRCAM axis played a significant role in regulating osteosarcoma progression, which may become a promising therapeutic method for osteosarcoma.
Insights
MicroRNA-338-3p acts as a tumor suppressor in osteosarcoma by inhibiting cell proliferation and migration. The KLF9/miR-338-3p/NRCAM pathway regulates osteosarcoma progression, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-338-3p (miR-338-3p) is a known tumor suppressor in various cancers.
- The role of miR-338-3p in osteosarcoma progression remains largely unexplored.
- Osteosarcoma is a primary bone malignancy with significant morbidity.
Purpose of the Study:
- To investigate the functional impact of miR-338-3p on osteosarcoma progression.
- To elucidate the underlying molecular mechanisms involving miR-338-3p in osteosarcoma.
- To identify potential therapeutic targets for osteosarcoma treatment.
Main Methods:
- Gene and miRNA expression analysis using qRT-PCR and Western blotting.
- Cellular proliferation, migration, and invasion assays (MTT, EdU, wound-healing, Transwell).
- Bioinformatic prediction of target genes and validation via dual-luciferase reporter assays.
Main Results:
- miR-338-3p expression is downregulated in osteosarcoma tissues.
- Overexpression of miR-338-3p significantly inhibits osteosarcoma cell proliferation, migration, and invasion.
- NRCAM acts as a direct target of miR-338-3p, mediating its anti-tumor effects.
- KLF9 positively regulates miR-338-3p expression in osteosarcoma cells.
Conclusions:
- The KLF9/miR-338-3p/NRCAM signaling axis is a critical regulator of osteosarcoma progression.
- Restoring miR-338-3p levels or targeting this axis shows therapeutic potential for osteosarcoma.
- This study identifies novel molecular players in osteosarcoma pathogenesis.
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