The MYC-independent effects of BET inhibitor JQ1 on super-enhancers in cancer

Abstract

MYC overexpression plays an important role in cancer progression and is a common feature of many cancer types. One reason is due to the invasion of super-enhancer regions by MYC upstream of oncogenes, often resulting in activation of oncogenic pathways and poorer prognosis. The activation of oncogenes under super-enhancer control can be repressed by Bromodomains and Extraterminal (BET) inhibitors, such as JQ1. It is however difficult to disentangle the MYC-dependent and MYC-independent effects of JQ1 on super-enhancer inhibition. To test the hypothesis that JQ1 does possess MYC-independent effects in super-enhancer inhibition, I induced MYC overexpression in U2OS, an osteosarcoma cell model that expresses high levels of MYC when treated with doxycycline and expresses MYC independent of JQ1. Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) was then utilized to study gene expression levels of four genes located within 100kb of MYC-bound super-enhancers, PFDN4, CEP55, TRAK1 and EFL1, in the presence and absence of JQ1. My findings suggest that JQ1 possesses MYC-independent effects in inhibiting super-enhancers, suggesting that JQ1 can be used in cancers that are mainly driven by other non-MYC super-enhancer associated oncogenes.