title: Ubiquitin ligase Siah1 promotes the migration and invasion of human glioma cells by regulating HIF-1α signaling under hypoxia.
abstract: It has been reported that by regulating PHD3 stability, Siah1 contributes to the abundance of hypoxia-inducible factor (HIF)-1α, thereby playing an important role in the cellular response to hypoxia. However, the expression level and functional significance of Siah1 in human malignant glioma, which is characterized by high migration and invasion potential, have never been investigated. We report here, that Siah1 was expressed highly in human glioma tissues compared with its expression in normal brain tissues and was correlated with advanced tumor status and stage. The knockdown of Siah1 by short-hairpin RNA severely suppressed the migration and invasion of human glioma U251 cells under hypoxia, while overexpression of Siah1 promoted it. Furthermore, we demonstrated that the glioma cell migration and invasion under hypoxia mediated by Siah1 was achieved by reducing the stability of PHD3, which protected the HIF-1α from degradation. These findings suggest that Siah1 plays important roles in the migration and invasion of human glioma cells under hypoxia, which may provide some guidance for the targeted therapy of human glioma based on the interference of the Siah1-PHD3-HIF-1α signaling pathway.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Bao
authors.initials: B
authors.lastname: Zheng
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics*; D000098563:Seven in Absentia Proteins
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C488894:EGLN3 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins