title: B-cell CLL/lymphoma 3 promotes glioma cell proliferation and inhibits apoptosis through the oncogenic STAT3 pathway.
abstract: Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues. Furthermore, high expression of BCL3 protein was confirmed by immunoblotting in glioma cells as compared with normal human astrocyte cell line. The positive expression of BCL3 was correlated with adverse prognostic features and reduced overall survival rate of glioma patients. BCL3 silencing resulted in prominent decreased proliferation, cell cycle arrest in G1 phase and increased apoptosis in U251 cells. In contrast, BCL3 overexpression in U87 cells remarkably facilitated proliferative ability and cell cycle progression and induced apoptosis. In vivo studies showed that BCL3 knockdown inhibited the tumor growth of U251 cells in a mouse xenograft model. Mechanistically, BCL3 positively regulated the abundance of STAT3, p-STAT3 and the downstream targets of STAT3 pathway including BCL2, MCL-1 and cyclin D1 in glioma cells. Furthermore, a positive correlation between BCL3 and STAT3 expression was observed in glioma specimens. Notably, we confirmed that STAT3 knockdown abolished the oncogenic roles of BCL3 in glioma. In conclusion, we suggest that BCL3 serves as an oncogene in glioma by modulating proliferation, cell cycle progression and apoptosis, and its oncogenic effects are mediated by the STAT3 signaling pathway.
authors.affiliation: Department of Neurosurgery, The People's Hospital of Gaozhou, Gaozhou, Guangdong 525200, P.R. China.
authors.forename: Jianheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The People's Hospital of Gaozhou, Gaozhou, Guangdong 525200, P.R. China.
authors.forename: Linfan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second People's Hospital of Guangxi Zhuang Autonomous Region, Guilin 541000, P.R. China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The People's Hospital of Gaozhou, Gaozhou, Guangdong 525200, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Gastroenterology, The People's Hospital of Gaozhou, Gaozhou, Guangdong 525200, P.R. China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001253:Astrocytes / Q000378:metabolism*; D000081242:B-Cell Lymphoma 3 Protein; D001921:Brain / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015996:Survival Rate; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; C530104:CCND1 protein, human; C000715470:MAS1 protein, human; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D019938:Cyclin D1