title: NF-κB induces miR-148a to sustain TGF-β/Smad signaling activation in glioblastoma.
abstract: BACKGROUND
  Inflammatory cytokines and transforming growth factor-β (TGF-β) are mutually inhibitory. However, hyperactivation of nuclear factor-κB (NF-κB) and TGF-β signaling both emerge in glioblastoma. Here, we report microRNA-148a (miR-148a) overexpression in glioblastoma and that miR-148a directly suppressed Quaking (QKI), a negative regulator of TGF-β signaling.
  
  
  METHODS
  We determined NF-κB and TGF-β/Smad signaling activity using pNF-κB-luc, pSMAD-luc, and control plasmids. The association between an RNA-induced silencing complex and QKI, mitogen-inducible gene 6 (MIG6), S-phase kinase-associated protein 1 (SKP1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was tested with microribonucleoprotein immunoprecipitation and real-time PCR. Xenograft tumors were established in the brains of nude mice.
  
  
  RESULTS
  QKI suppression induced an aggressive phenotype of glioblastoma cells both in vitro and in vivo. Interestingly, we found that NF-κB induced miR-148a expression, leading to enhanced-strength and prolonged-duration TGF-β/Smad signaling. Notably, these findings were consistent with the significant correlation between miR-148a levels with NF-κB hyperactivation and activated TGF-β/Smad signaling in a cohort of human glioblastoma specimens.
  
  
  CONCLUSIONS
  These findings uncover a plausible mechanism for NF-κB-sustained TGF-β/Smad activation via miR-148a in glioblastoma, and may suggest a new target for clinical intervention in human cancer.
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tian He Road, Tian He District, Guangzhou, Guangdong, 510630, China. doctorwanghui@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, 518052, China. panjianqingsz@163.com.|Guangzhou Biocare Cancer Institute, Guangzhou, 510663, China. panjianqingsz@163.com.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Pan
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tian He Road, Tian He District, Guangzhou, Guangdong, 510630, China. lawrence-luo@126.com.
authors.forename: Lun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tian He Road, Tian He District, Guangzhou, Guangdong, 510630, China. ningxinjie@163.com.
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Ning
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tian He Road, Tian He District, Guangzhou, Guangdong, 510630, China. yezhpzhshsy@yahoo.com.cn.
authors.forename: Zhuo-Peng
authors.initials: ZP
authors.lastname: Ye
authors.affiliation: Guangzhou Biocare Cancer Institute, Guangzhou, 510663, China. macx84@gmail.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tian He Road, Tian He District, Guangzhou, Guangdong, 510630, China. dr-lws@21cn.com.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C490832:QKI protein, human; D016601:RNA-Binding Proteins; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; D051785:Smad Proteins; D016212:Transforming Growth Factor beta