RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC

V. Selvarajan, M. Osato, G. S.S. Nah, J. Yan, T. H. Chung, D. C.C. Voon, Y. Ito, Maria Francisca Ham, M. Salto-Tellez, N. Shimizu, S. N. Choo, S. Fan, W. J. Chng, S. B. Ng

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


RUNX3, runt-domain transcription factor, is a master regulator of gene expression in major developmental pathways. It acts as a tumor suppressor in many cancers but is oncogenic in certain tumors. We observed upregulation of RUNX3 mRNA and protein expression in nasal-type extranodal natural killer (NK)/T-cell lymphoma (NKTL) patient samples and NKTL cell lines compared to normal NK cells. RUNX3 silenced NKTL cells showed increased apoptosis and reduced cell proliferation. Potential binding sites for MYC were identified in the RUNX3 enhancer region. Chromatin immunoprecipitation-quantitative PCR revealed binding activity between MYC and RUNX3. Co-transfection of the MYC expression vector with RUNX3 enhancer reporter plasmid resulted in activation of RUNX3 enhancer indicating that MYC positively regulates RUNX3 transcription in NKTL cell lines. Treatment with a small-molecule MYC inhibitor (JQ1) caused significant downregulation of MYC and RUNX3, leading to apoptosis in NKTL cells. The growth inhibition resulting from depletion of MYC by JQ1 was rescued by ectopic MYC expression. In summary, our study identified RUNX3 overexpression in NKTL with functional oncogenic properties. We further delineate that MYC may be an important upstream driver of RUNX3 upregulation and since MYC is upregulated in NKTL, further study on the employment of MYC inhibition as a therapeutic strategy is warranted.

Original languageEnglish
Pages (from-to)2219-2227
Number of pages9
Issue number10
Publication statusPublished - 1 Oct 2017


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