title: Role of PHLPP1 in inflammation response: Its loss contributes to gliomas development and progression.
abstract: PH domain leucine-rich repeats protein phosphatase 1(PHLPP1) belongs to a novel family of Ser/Thr protein phosphatases: PHLPP serves as tumor suppressor in several cancers. However, little knowledge about the expression of PHLPP1 in human glioma tumor tissue and its role in inflammation response in glioma cells was known. Glioma samples were obtained from a total of 37 patients including 16 males and 21 females with surgical removal of the brain tumor. PHLPP1 protein and inflammatory cytokines were measured by Western blot analysis and immunohistochemistry while mRNA was determined by RT-PCR. The levels of inflammatory cytokines including TNF-α, IL-17, IL-1β in U251 glioma cells were evaluated by siRNA PHLPP1 and PHLPP1 addition. The loss of PHLPP1 expression occurs at high frequency in human gliomas. The highest mean values of PHLPP1 mRNA and protein were found in non-glioma brain tissues whereas the lowest mean values were found in those in glioblastoma with an increase of TNF-α, IL-17, IL-1β (p<0.05). PHLPP1 expression in human glioma was associated negatively with the severity of the tumor and inflammatory cytokines. siRNA PHLPP1 could increase the levels of inflammatory cytokines in U251 glioma cells while PHLPP1 addition could inhibit significantly inflammatory cytokines. We concluded that PHLPP1 played a suppression role in inflammatory response of glioma. The present study indicated that PHLPP1 could be used as a predictor for the prediction of the patients or as a therapeutic target for the treatment of human glioma.
authors.affiliation: Brain Hospital, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. Electronic address: tengdc2011@163.com.
authors.forename: Da-Cai
authors.initials: DC
authors.lastname: Teng
authors.affiliation: Department of Endocrinology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Yi-Qiang
authors.initials: YQ
authors.lastname: An
authors.affiliation: Neural Biology Research Center, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Zhong-Hao
authors.initials: ZH
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Yong-Chao
authors.initials: YC
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D063646:Carcinogenesis; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases
keywords: Glioma; Inflammation; PHLPP1; Tumor suppressors