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Updated: May 3, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Stat3 upregulates leucine-rich repeat-containing g protein-coupled receptor 4 expression in osteosarcoma cells
Jia Liu1, Wei Wei2, Chang-An Guo1
1Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Abstract:
The activation of signal transducer and activator of transcription 3 (Stat3) signaling is the common hallmark in various human cancers including osteosarcoma. In the present study, according to PCR-based microarrays using cDNA prepared from interleukin-6 (IL-6) treated osteosarcoma cells, we found that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) was a transcriptional target of Stat3. Overexpression of Stat3 promoted LGR4 expression, while its deficiency using small interfering RNA (siRNA) reduced LGR4 expression. Furthermore, we identified a Stat3 binding motif located at -556 to -549 bp in the LGR4 promoter that is able to interact with Stat3. Thus, our results suggest a previously unknown Stat3-LGR4 molecular network, which may control osteosarcoma development and progression.
Insights
Signal transducer and activator of transcription 3 (Stat3) promotes leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) expression in osteosarcoma. This Stat3-LGR4 network may drive cancer progression.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Signal transducer and activator of transcription 3 (Stat3) activation is a common feature in human cancers.
- Osteosarcoma is a prevalent bone cancer where Stat3 signaling is frequently implicated.
Purpose of the Study:
- To investigate the relationship between Stat3 signaling and gene expression in osteosarcoma.
- To identify novel transcriptional targets of Stat3 in osteosarcoma cells.
Main Methods:
- PCR-based microarrays were employed using cDNA from interleukin-6 (IL-6) treated osteosarcoma cells.
- Small interfering RNA (siRNA) was used to assess the effect of Stat3 deficiency on gene expression.
- Bioinformatic analysis identified a Stat3 binding motif in the LGR4 promoter region.
Main Results:
- Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) was identified as a transcriptional target of Stat3.
- Stat3 overexpression enhanced LGR4 expression, while Stat3 deficiency reduced it.
- A functional Stat3 binding motif was confirmed in the LGR4 promoter (-556 to -549 bp).
Conclusions:
- A novel molecular network involving Stat3 and LGR4 in osteosarcoma has been elucidated.
- This Stat3-LGR4 interaction is a potential regulator of osteosarcoma development and progression.
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