Related Experiment Video
Updated: Jan 1, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells
Joerg Fellenberg1, Burkhard Lehner1, Heiner Saehr1
1Center for Orthopedics, Trauma Surgery and Paraplegiology, University of Heidelberg, 69118 Heidelberg, Germany.
Abstract:
Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.
Insights
Restoring miR-127-3p and miR-376a-3p microRNAs suppressed osteosarcoma cell proliferation and tumor growth. These microRNAs show potential as novel therapeutic targets for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma survival rates have stagnated despite advances in chemotherapy.
- MicroRNAs (miRNAs) are implicated in cancer development and aberrant miRNA expression is observed in osteosarcoma.
- Novel therapeutic strategies targeting miRNAs are needed for osteosarcoma treatment.
Purpose of the Study:
- To investigate the tumor suppressor roles of miR-127-3p and miR-376a-3p in osteosarcoma.
- To evaluate the therapeutic potential of restoring these miRNAs in osteosarcoma.
Main Methods:
- Silencing of miR-127-3p and miR-376a-3p was identified in osteosarcoma cell lines and tissues.
- Osteosarcoma cells were transfected with miR-127-3p and miR-376a-3p mimics.
- In vitro proliferation and colony formation assays were performed.
- In vivo tumor growth was assessed using a chicken chorioallantoic membrane (CAM) assay.
Main Results:
- Restoration of miR-127-3p and miR-376a-3p significantly inhibited osteosarcoma cell proliferation and colony formation in vitro.
- No significant effects on cell cycle or apoptosis were observed upon miRNA restoration.
- In vivo CAM assays showed reduced tumor take rates and tumor volumes in cells transfected with miR-127-3p and miR-376a-3p mimics.
- Cumulative tumor volumes were significantly decreased to 41% and 54% compared to wildtype cells.
Conclusions:
- miR-127-3p and miR-376a-3p function as tumor suppressors in osteosarcoma.
- Restoration of these miRNAs inhibits osteosarcoma cell proliferation and tumor growth.
- miR-127-3p and miR-376a-3p represent promising therapeutic targets for osteosarcoma treatment.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
01:22MicroRNAs
01:22MicroRNAs
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...