Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/144369
Title: CHARACTERIZATION OF THE BIOLOGICAL AND CLINICAL RELEVANCE OF RUNX GENES IN NATURAL KILLER/T-CELL LYMPHOMA
Authors: VIKNESVARAN SELVARAJAN
Keywords: NK/T cell lymphoma, RUNX3, MYC, oncogene, transcription factor, small molecule inhibitor
Issue Date: 22-Jan-2016
Citation: VIKNESVARAN SELVARAJAN (2016-01-22). CHARACTERIZATION OF THE BIOLOGICAL AND CLINICAL RELEVANCE OF RUNX GENES IN NATURAL KILLER/T-CELL LYMPHOMA. ScholarBank@NUS Repository.
Abstract: RUNX3 PLAY PIVOTAL ROLES IN CELL PROLIFERATION AND DIFFERENTIATION IN HUMANS. IT ACTS AS A TUMOR SUPPRESSER IN MANY CANCERS BUT IS ONCOGENIC IN CERTAIN TUMORS. RUNX3 EXPRESSION WAS UPREGULATED IN NASAL-TYPE EXTRANODAL NK/T-CELL LYMPHOMA (NKTCL) PATIENT SAMPLES AND NKTCL CELL LINES. CHIP-QPCR REVEALED BINDING ACTIVITY BETWEEN MYC AND RUNX3, AND TRANSFECTION WITH MYC EXPRESSION VECTOR ACTIVATED RUNX3 ENHANCER ACTIVITY. RESULTS INDICATE THAT MYC POSITIVELY REGULATES RUNX3 TRANSCRIPTION IN NKTCL CELL LINES. TREATMENT WITH A SMALL-MOLECULE MYC INHIBITOR (JQ1) CAUSED SIGNIFICANT DOWNREGULATION OF MYC AND RUNX3 IN A DOSE-DEPENDENT MANNER, LEADING TO APOPTOSIS IN NKTCL CELL LINES. OUR STUDY IDENTIFIED RUNX3 OVEREXPRESSION IN NKTCL WITH FUNCTIONAL ONCOGENIC PROPERTIES. WE FURTHER DELINEATE THAT MYC MAY BE AN IMPORTANT UPSTREAM DRIVER OF RUNX3 UPREGULATION AND SINCE MYC IS UPREGULATED IN NKTCL FROM OUR PREVIOUS STUDY, THE USE OF NOVEL INHIBITORS SUCH AS JQ1 MAY BE AN EFFECTIVE STRATEGY IN NKTCL.
URI: http://scholarbank.nus.edu.sg/handle/10635/144369
Appears in Collections:Ph.D Theses (Open)

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