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Updated: Sep 23, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
miR-29a-3p mitigates the development of osteosarcoma through modulating IGF1 mediated PI3k/Akt/FOXO3 pathway by
Song Qi1, Li Xu1, Yongyuan Han2
1Department of Trauma Surgery, Wuhan No 1 Hospital, Wuhan, Hubei, China.
Abstract:
Osteosarcoma (OS), occurring in mesenchymal tissues and with a high degree of malignancy, is most common in children and adolescents. At present, we intend to figure out the expression and functions of miR-29a-3p in OS development. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to monitor the expression of miR-29a-3p and IGF1 in OS tissues and adjacent non-tumor tissues. Then, the 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, colony formation experiment, western blot and Transwell assay were conducted to validate OS cell proliferation, colony formation ability, apoptosis, migration and invasion. Next, the association between miR-29a-3p and IGF1 was corroborated by the dual-luciferase reporter assay and the Pearson correlation analysis. Finally, WB was implemented to test the levels of autophagy-related proteins LC3-I/LC3-II, Beclin-1, p62, and the IGF-1 R/PI3k/Akt/FOXO3 axis in OS cells. As a result, miR-29a-3p was down-regulated in OS tissues (versus adjacent non-tumor tissues) and OS cell lines. Overexpressing miR-29a-3p aggravated apoptosis, dampened cell proliferation, colony formation, migration and invasion, and promoted autophagy of OS cells. IGF1 was identified as a target of miR-29a-3p. IGF1 induced oncogenic effects in OS by activating IGF-1 R/ PI3k/Akt pathway, and it dampened the tumor-suppressive effect of miR-29a-3p on OS. Taken together, miR-29a-3p repressed the OS evolvement through inducing autophagy and inhibiting IGF1 mediated PI3k/Akt/FOXO3 pathway.
Insights
MicroRNA-29a-3p (miR-29a-3p) is downregulated in osteosarcoma (OS). Restoring miR-29a-3p inhibits OS cell growth and metastasis by promoting autophagy and suppressing the IGF1 signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is a highly malignant bone tumor common in children and adolescents.
- Understanding the molecular mechanisms regulating OS development is crucial for targeted therapies.
Purpose of the Study:
- To investigate the expression and functional role of microRNA-29a-3p (miR-29a-3p) in osteosarcoma (OS).
- To elucidate the relationship between miR-29a-3p and Insulin-like Growth Factor 1 (IGF1) in OS progression.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) for gene expression analysis.
- Cell proliferation, apoptosis, migration, and invasion assays (MTT, colony formation, Transwell).
- Dual-luciferase reporter assay and Western blot to confirm molecular interactions and pathway activation.
Main Results:
- miR-29a-3p was significantly downregulated in OS tissues and cell lines.
- Overexpression of miR-29a-3p suppressed OS cell proliferation, migration, invasion, and colony formation, while promoting apoptosis and autophagy.
- IGF1 was identified as a direct target of miR-29a-3p, and IGF1 promoted OS progression via the IGF-1R/PI3k/Akt/FOXO3 pathway.
Conclusions:
- miR-29a-3p acts as a tumor suppressor in OS by inhibiting cell proliferation, migration, and invasion.
- miR-29a-3p represses OS development by inducing autophagy and suppressing the IGF1-mediated PI3k/Akt/FOXO3 pathway.
- Targeting miR-29a-3p or the IGF1 pathway may offer therapeutic strategies for osteosarcoma.
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