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Mol Cancer DOI:10.1186/1476-4598-14-2

NF-κB induces miR-148a to sustain TGF-β/Smad signaling activation in glioblastoma.

Publication TypeJournal Article
Year of Publication2015
AuthorsWang, H, Pan, J-Q, Luo, L, Ning, X-J, Ye, Z-P, Yu, Z, Li, W-S
JournalMol Cancer
Volume14
Pages2
Date Published2015 Feb 11
ISSN1476-4598
KeywordsAnimals, Base Sequence, Brain Neoplasms, Carcinogenesis, Cell Line, Tumor, Disease Progression, Glioblastoma, Humans, Mice, Nude, MicroRNAs, Molecular Sequence Data, Neoplasm Invasiveness, Neovascularization, Pathologic, NF-kappa B, Phenotype, Prognosis, RNA-Binding Proteins, S-Phase Kinase-Associated Proteins, Signal Transduction, Smad Proteins, Transforming Growth Factor beta, Up-Regulation
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.

DOI10.1186/1476-4598-14-2
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25971746?dopt=Abstract

Alternate JournalMol. Cancer
PubMed ID25971746
PubMed Central IDPMC4429406