Stat3 upregulates leucine-rich repeat-containing g protein-coupled receptor 4 expression in osteosarcoma cells.
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.
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jia
J
Liu
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Wei
W
Wei
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chang-An
CA
Guo
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Ning
N
Han
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jian-feng
JF
Pan
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Teng
T
Fei
Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zuo-qin
ZQ
Yan
D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D046228:Microarray Analysis; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; C411562:LGR4 protein, human; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human