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8th World Congress on Epigenetics and Chromosome

Zurich, Switzerland

Xingsheng Shu,

Xingsheng Shu,

Shenzhen University, China

Title: MECOM-regulated distal super-enhancer activates ETS2 transcription and promotes colorectal cancer progression

Biography

Biography: Xingsheng Shu,

Abstract

It has long been documented that abnormal activities of distal cis-regulatory elements such as enhancers
contribute to the intitation and progression of cancer. Recently, super-enhancer hijacking was found to be
esstential for the activation of certain oncogenes. However, the mechanism of action for most tumor-specific
super-enhancers still largely remain elusive. Here, we report that a potential oncogene ETS2 was activated
by a super-enhancer located at its 3’ distal region in colorectal cancer (CRC). The super-enhancer physcially
interacts with ETS2 promoter fragments and is required for transription activation of ETS2. Intriguingly, we
found that a eQTL site for ETS2 resides in this super-enhancer and genetic variation at the SNP potentailly
abolished the binding of a well-known oncogenic trancritpion factor MECOM. Consistently, the expression
of MECOM and ETS2 correlated well with each other in CRC cell lines and multiple CRC datasets and silecning
of MECOM induced downregulation of ETS2. Moreover, the expression of enhancer RNA (eRNA) from the
ETS2 super-enhancer also correlated with the expression of ETS2 in primary CRC samples. Finally, silencing
of both MECOM and ETS2 lead to the inhibition of proliferation, migration and sphere formation of CRC
cells. Taken together, we uncovered a novel MECOM-super enhancer-ETS2 regulatory axis that might be
crucial for activating oncogenic ETS2 in CRC.