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Updated: May 11, 2026

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MicroRNA-376c inhibits cell proliferation and invasion in osteosarcoma by targeting to transforming growth
1Department of Orthopedics, Second Xiangya Hospital, Central South University, Changsha, China.
Abstract:
MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-376c expression level was decreased while transforming growth factor-alpha (TGFA) mRNA expression levels were increased in osteosarcoma tissues and cell lines, and we identified TGFA as a novel direct target of miR-376c. Overexpression of miR-376c suppressed TGFA expression and the expression of its downstream signaling molecule such as epidermal growth factor receptor, and attenuated cell proliferation and invasion. Forced expression of TGFA could partly rescue the inhibitory effect of miR-376c in the cells. Taken together, these findings will shed light on the role and mechanism of miR-376c in regulating osteosarcoma cell growth via miR-376c/TGFA axis, and miR-376c may serve as a potential therapeutic target in osteosarcoma in the future.
Insights
MicroRNA-376c (miR-376c) inhibits osteosarcoma growth by targeting transforming growth factor-alpha (TGFA). Decreased miR-376c and increased TGFA correlate with osteosarcoma, suggesting miR-376c as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs regulate gene expression by targeting messenger RNAs (mRNAs).
- Dysregulation of microRNAs is implicated in various cancers, including osteosarcoma.
Purpose of the Study:
- To investigate the role of miR-376c in osteosarcoma.
- To identify and characterize the downstream targets of miR-376c in osteosarcoma cells.
Main Methods:
- Quantitative real-time PCR to measure miR-376c and TGFA mRNA levels.
- Luciferase reporter assays to confirm direct targeting of TGFA by miR-376c.
- Cell proliferation and invasion assays to assess functional effects.
Main Results:
- miR-376c expression was decreased, while TGFA mRNA was increased in osteosarcoma tissues and cell lines.
- TGFA was identified as a direct target of miR-376c.
- Overexpression of miR-376c suppressed TGFA expression, inhibited cell proliferation and invasion, and reduced downstream signaling molecules like epidermal growth factor receptor.
- Forced TGFA expression partially rescued the inhibitory effects of miR-376c.
Conclusions:
- miR-376c acts as a tumor suppressor in osteosarcoma by targeting TGFA.
- The miR-376c/TGFA axis plays a crucial role in regulating osteosarcoma cell growth and invasion.
- miR-376c holds potential as a therapeutic target for osteosarcoma treatment.
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