title: BASI, a potent small molecular inhibitor, inhibits glioblastoma progression by targeting microRNA-mediated β-catenin signaling.
abstract: OBJECTIVE
  The nuclear localization of β-catenin, a mediator of canonical Wnt signaling, has been indicated in a variety of cancers and is frequently related to tumor progression and metastasis. Therefore, targeting β-catenin is an attractive therapeutic strategy for cancers.
  
  
  METHODS
  Herein, we identified a natural, small molecule inhibitor of β-catenin signaling, BASI, and evaluated its therapeutic efficacy both in vitro and in orthotopic mouse models of glioma.
  
  
  RESULTS
  BASI significantly suppressed proliferation and invasion and induced apoptosis in glioblastoma cells and resulted in the remarkable attenuation of orthotopic tumor growth in vivo. Furthermore, we found that BASI altered the expression of several microRNAs, which mediated the posttranscriptional silencing of β-catenin expression either directly or indirectly through a von Hippel-Lindau (VHL)-mediated β-catenin degradation pattern.
  
  
  CONCLUSIONS
  Taken together, our findings offer preclinical validation of BASI as a promising new type of β-catenin inhibitor with a mechanism of inhibition that has broad potential for the improved treatment of glioblastoma.
authors.affiliation: Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China; Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in the Central Nervous System, Ministry of Education Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin, China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Shi
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Qian
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Kai-Liang
authors.initials: KL
authors.lastname: Zhang
authors.forename: Lu-Yue
authors.initials: LY
authors.lastname: Chen
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Zhang
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D050882:CREB-Binding Protein / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C092772:barley alpha-amylase-subtilisin inhibitor; D051176:beta Catenin; D014360:Trypsin Inhibitor, Kunitz Soybean; D050882:CREB-Binding Protein; C494363:CREBBP protein, human
keywords: BASI; Glioblastoma; Inhibitor; microRNA; β-Catenin