title: Overexpression of iASPP-SV in glioma is associated with poor prognosis by promoting cell viability and antagonizing apoptosis.
abstract: Inhibitor of apoptosis-stimulating protein of p53 (iASPP), encoded by PPP1R13L gene, is often overexpressed in human cancers. From the PPP1R13L gene, at least two isoforms, iASPP-L and iASPP-SV, are produced through alternative splicing. However, the role of these isoforms in glioma is still elusive. In this study, we examined the expression of iASPP-SV in astrocytic glioma tissues with different grades and normal human cerebral tissues. The result showed a higher messenger RNA (mRNA) expression level of iASPP-SV in astrocytic glioma patients with World Health Organization (WHO) grade II to IV in comparison to the normal controls. Additionally, mRNA expression level of iASPP-SV was gradually increased with the raise of the grade in glioma. High mRNA expression level of iASPP-SV was significantly associated with malignant WHO grades (P < 0.001). The protein expression level of iASPP-SV was consistent with the mRNA expression level. The Kaplan-Meier analysis revealed that high iASPP-SV mRNA expression significantly affected overall survival and progression-free survival (both P < 0.001). Furthermore, multivariate analysis indicated that the mRNA expression of iASPP-SV was an independent prognostic marker in glioma (P < 0.001). To further explore the role of iASPP-SV in glioma, U87 cells were transfected with iASPP-SV by lentivirus and then treated with temozolomide (TMZ). Overexpression of iASPP-SV promoted the cell viability and downregulated the expression of pro-apoptosis genes (Bax, Puma, p21, and Noxa) to inhibit apoptosis induced by TMZ. Our study provides the first evidence that high iASPP-SV expression may be a novel prognostic factor and therapeutic target for glioma.
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.|Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, People's Republic of China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Xiang, Beijing, 100730, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.|Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.|Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, People's Republic of China.
authors.forename: Shaohong
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong, 261031, People's Republic of China.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.|Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, People's Republic of China.|Department of Neurosurgery, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong, 261031, People's Republic of China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Liu
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.|Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, People's Republic of China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, People's Republic of China.|Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, People's Republic of China.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Xiang, Beijing, 100730, People's Republic of China. zshangfeng@126.com.
authors.forename: Shangfeng
authors.identifier: http://orcid.org/0000-0003-0250-5566
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011379:Prognosis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000077204:Temozolomide
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Apoptosis; Glioma; Isoform; Prognosis; Survival; iASPP