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2018 ; 6
(ä): 11
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Super enhancer inhibitors suppress MYC driven transcriptional amplification and
tumor progression in osteosarcoma
#MMPMID29644114
Chen D
; Zhao Z
; Huang Z
; Chen DC
; Zhu XX
; Wang YZ
; Yan YW
; Tang S
; Madhavan S
; Ni W
; Huang ZP
; Li W
; Ji W
; Shen H
; Lin S
; Jiang YZ
Bone Res
2018[]; 6
(ä): 11
PMID29644114
show ga
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young
adults. The causes of osteosarcoma are heterogeneous and still not fully
understood. Identification of novel, important oncogenic factors in osteosarcoma
and development of better, effective therapeutic approaches are in urgent need
for better treatment of osteosarcoma patients. In this study, we uncovered that
the oncogene MYC is significantly upregulated in metastastic osteosarcoma
samples. In addition, high MYC expression is associated with poor survival of
osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most
of the osteosarcoma super enhancer genes are bound by MYC. Treatment of
osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively
suppresses the proliferation, migration, and invasion of osteosarcoma cells.
Mechanistically, THZ1 treatment suppresses a large group of super enhancer
containing MYC target genes including CDK6 and TGFB2. These findings revealed
that the MYC-driven super enhancer signaling is crucial for the osteosarcoma
tumorigenesis and targeting the MYC/super enhancer axis represents as a promising
therapeutic strategy for treatment of osteosarcoma patients.