title: KIAA0247 suppresses the proliferation, angiogenesis and promote apoptosis of human glioma through inactivation of the AKT and Stat3 signaling pathway.
abstract: Gliomas are the most common and aggressive type of primary adult brain tumors. Although KIAA0247 previously is a speculated target of the tumor suppressor gene, little is known about the association between KIAA0247 and glioma. In this study, we clearly demonstrate that KIAA0247 expression is decreased in glioma and was negatively correlated with the histologic grade. Overexpression of KIAA0247 in glioma cells inhibits proliferation, angiogenesis and promoted apoptosis of human glioma cells in vitro. In contrast, knockdown of KIAA0247 increases the proliferation, angiogenesis and decreases apoptosis of these cells. In a tumor xenograft model, overexpression of KIAA0247 suppresses tumor growth of glioma cells in vivo, while KIAA0247 knockdown promotes the tumor growth. Mechanistically, overexpression of KIAA0247 is able to inhibit phosphorylation of AKT and Stat3 in glioma cells, resulting in inactivation of the AKT and Stat3 signaling pathways, this ultimately decreases the expression of PCNA, CyclinD1, Bcl2 and VEGF. Collectively, these data indicate that KIAA0247 may work as a tumor suppressor gene in glioma and a promising therapeutic target for gliomas.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pi
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003165:Complement System Proteins / Q000502:physiology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; C551654:SUSD6 protein, human; D025521:Tumor Suppressor Proteins; D003165:Complement System Proteins; D051057:Proto-Oncogene Proteins c-akt
keywords: KIAA0247; angiogenesis; cell apoptosis; cell proliferation; glioma