title: PARP3 interacts with FoxM1 to confer glioblastoma cell radioresistance.
abstract: Poly(ADP-ribose) polymerase 3 (PARP3), a critical player in cellular response to DNA double-strand breaks (DSBs), plays an essential role in the maintenance of genome integrity. However, the role of PARP3 in tumorigenesis especially in glioblastoma remains largely unknown. In the present study, we found that the mRNA and protein levels of PARP3 were upregulated in primary glioblastoma tissues. Knockdown of PARP3 expression by lentivirus-based shRNA decreased cell glioblastoma proliferation and inhibited tumor growth in vivo by using a xenograft mouse model. Furthermore, we found that silencing the expression of PARP3 resulted in a synergistic radiosensitizing effect when combined with radiotherapy in glioblastoma cell lines. At the molecular level, we found that PARP3 interacted with FoxM1 to enhance its transcriptional activity and conferred glioblastoma cell radioresistance. Thus, our data suggest that PARP3 could be a therapeutic target to overcome radioresistance in glioblastoma.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi, 710004, People's Republic of China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Quan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi, 710061, People's Republic of China. qjjieqjj@126.com.
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shanxi, 710004, People's Republic of China.
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Qu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; C480979:PARP3 protein, human; D011065:Poly(ADP-ribose) Polymerases
keywords: Apoptosis; Glioblastoma; PARP3; Radioresistance