title: Silencing of Eag1 Gene Inhibits Osteosarcoma Proliferation and Migration by Targeting STAT3-VEGF Pathway.
abstract: So far, the role of Ether à go-go 1 (Eag1) potassium channels in migration and invasion progression of cancers remains elusive. In the present study, the effects of Eag1 knockdown on osteosarcoma cell proliferation, growth, and apoptosis were examined. Then, we evaluated the effects of Eag1 silencing on osteosarcoma cell migration and invasion. In addition, we detected the expression of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) in osteosarcoma cell treated with Eag1 small interfering RNAs (siRNAs). Finally, STAT3 siRNA was employed to determine the influence of downregulation of STAT3 on cell proliferation and migration. The results showed that knockdown of Eag1 significantly suppressed osteosarcoma cell proliferation and osteosarcoma xenografts growth. However, Eag1 silencing had little effect on cell apoptosis. Additionally, osteosarcoma cell adhesion, migration, and invasion were also potently attenuated. Notably, the expression levels of VEGF decreased evidently upon Eag1 siRNAs treatment, paralleled with reductions in the expression levels of STAT3. Moreover, a similar pattern was observed in osteosarcoma cell proliferation and migration suppression between STAT3 siRNA and Eag1 siRNAs groups. Our data indicated that Eag1 promotes osteosarcoma proliferation and migration, at least in part, by targeting STAT3-VEGF pathway.
authors.affiliation: Department of Neurology, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, The Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China.
authors.forename: Wengrong
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Central Laboratory, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, China.
authors.forename: Yuanfu
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Orthopaedics, The Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, The Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A