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Poster presentation 1

506 - miR-17 ∼ 92 activates the canonical NF-κB signaling by targeting TNFAIP3, CYLD and Rnf11 in ABC-DLBCL lymphoma


19 Dec 2015


Poster presentation 1


Xianhuo Wang


Annals of Oncology (2015) 26 (suppl_9): 85-92. 10.1093/annonc/mdv526


X. Wang1, H. Wang2, C. Bi3, X. Zhang4, X. Huang3, X. Zhang3, J. Iqbal3, G.W. Wright5, L.M. Staudt6, W.C. Chan7, T.W. McKeithan7, P. Wang2, H. Zhang2, K. Fu3

Author affiliations

  • 1 Department Of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, 300060 - Tianjin/CN
  • 2 Department Of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin/CN
  • 3 Department Of Pathology And Microbiology And Internal Medicine, University of Nebraska Medical Center, Omaha/US
  • 4 Department Of Pediatrics, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin/CN
  • 5 Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethlehem/US
  • 6 Lymphoid Malignancies Branch, Center for Cancer Research-National Cancer Institute, Bethesda/US
  • 7 Department Of Pathology, City of Hope, Duarte/US


Abstract 506


ABC-DLBCL is a aggressive lymphoma characterized by constitutive NF-κB activation, but whether miRNAs dysfunction contributes to this event remains unclear. The purpose of this study is to reveal the correlations between miR-17 ∼ 92 and NF-κB signaling in ABC-DLBCL


MiRNA array platform was used for informatics and statistical interrelations. Potential miR-17 ∼ 92 targets were identified and validated using computational prediction and reporter gene assays. The activity of NF-κB signaling was determined by reporter assays. The expression and regulation of miR-17 ∼ 92 were studied using real-time quantitative PCR and Western blotting. Cell proliferation, cycle and apoptosis were detected by MTS and flow cytometry. Ubiquitination was studied by co-immunoprecipitation.


The interactions between NF-κB signaling and miR-17 ∼ 92 existed in ABC-DLBCL patients. Several important NF-κB negative regulators including TNFAIP3, CYLD and Rnf11 were predicted and validated to be targets of miR-17 ∼ 92. Knock-down of miR-17 ∼ 92 could suppress NF-κB activity and elevate targets protein expression in 293T cells. Furthermore, overexpression of miR-17 ∼ 92 could also decrease targets protein level in ABC-DLBCL cells. Conditional overexpression of miR-17 ∼ 92 could promote cells growth, accelerate G1/G0 phase to S phase transition, and suppress NF-κB inhibitor-induced apoptosis. Conversely, knock-down of miR-17 ∼ 92 could inhibit cells growth and sensitize cells to NF-κB inhibitor-induced apoptosis. MiR-17 ∼ 92 could induce IκB-α and NF-κB p65 phosphorylation and aberrant expression of NF-κB transcriptional target genes. However, miR-17 ∼ 92 did not regulate NF-κB p52/p100 phosphorylation. Overexpression of miR-17 ∼ 92 enhanced K63-linked ubiquitination and reduced K48-linked ubiquitination of RIP1. High expression level of miR-17 ∼ 92 was associated with poorer survival in ABC-DLBCL patients.


Our results uncovered a novel mechanism for canonical but not non-canonical NF-κB pathway by modulation of miR-17 ∼ 92 in ABC-DLBCL, and suggested that targeting miR-17 ∼ 92 might be novel bio-therapeutic strategies for ABC-DLBCL patients.

Clinical trial identification

The study was approved by the Institutional Review Board of the University of Nebraska Medical Center.


All authors have declared no conflicts of interest.

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