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.
Highlights
Oncogenes and tumor suppressors play critical roles in the tumorigenesis [1]
We demonstrate that signal transducer and activator of transcription 3 (Stat3) regulates leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) expression in two human osteosarcoma cells
We identified a potential Stat3 binding site in the promoter region of LGR4 gene
Summary
Oncogenes and tumor suppressors play critical roles in the tumorigenesis [1]. Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that can promote tumor progression, and it is usually activated in several types of human cancer cells [2]. Stat signaling induced by its ligands such as interleukin-6, growth factors, is tightly regulated, owing to the existence of negative feedback mechanisms including induction of suppressor of cytokine signaling (SOCS) proteins [3]. In cancer cells, aberrant IL-6/Stat signaling has been implied as a critical mechanism for tumor initiation, proliferation, and metastasis [4, 5]. To better understand the roles of Stat it will be helpful to seek new therapeutics for human cancers including osteosarcoma
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