Please use this identifier to cite or link to this item: https://doi.org/10.1038/leu.2017.40
Title: RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC
Authors: Selvarajan, V 
Osato, M 
Nah, GSS 
Yan, J 
Chung, T-H 
Voon, DC-C 
Ito, Y 
Ham, MF
Salto-Tellez, M 
Shimizu, N
Choo, S-N
Fan, S
Chng, W-J 
Ng, S-B 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Hematology
EPSTEIN-BARR-VIRUS
GENE-EXPRESSION PROFILES
C-MYC
PROTEIN MISLOCALIZATION
TUMOR-SUPPRESSOR
BET BROMODOMAINS
OVARIAN-CANCER
FAMILY GENES
IN-VIVO
GROWTH
Issue Date: 1-Oct-2017
Publisher: NATURE PUBLISHING GROUP
Citation: Selvarajan, V, Osato, M, Nah, GSS, Yan, J, Chung, T-H, Voon, DC-C, Ito, Y, Ham, MF, Salto-Tellez, M, Shimizu, N, Choo, S-N, Fan, S, Chng, W-J, Ng, S-B (2017-10-01). RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC. LEUKEMIA 31 (10) : 2219-2227. ScholarBank@NUS Repository. https://doi.org/10.1038/leu.2017.40
Abstract: 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.
Source Title: LEUKEMIA
URI: https://scholarbank.nus.edu.sg/handle/10635/206148
ISSN: 08876924
14765551
DOI: 10.1038/leu.2017.40
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