Super-enhancer-associated oncogenes as novel therapeutic targets in osteosarcoma (ChIP-seq)

GSE134604 Super-enhancer-associated oncogenes as novel therapeutic targets in osteosarcoma (ChIP-seq): Contributors : Jiajun Zhang ; Weihai Liu ; Changye Zou ; Zhiqiang Zhao ; Yuanying Lai ; Zhi Shi ; Xianbiao Xie ; Gang Huang ; Yongqian Wang ; Xuelin Zhang ; Zeipei Fan ; Qiao Su ; Junqiang Yin ; Jingnan Shen

Series Type : Genome binding/occupancy profiling by high throughput sequencing

Organism : Homo sapiens

Despite the development of diagnostic and advanced treatment strategies, the prognosis of patients with osteosarcoma remains poor. A limited understanding of the pathogenesis of osteosarcomas has impeded any improvement in patient outcomes over the past 4 decades. It is thus urgent to identify novel effective targets and treatment regimens for osteosarcoma patients. In this study we delineated the super-enhancer landscape in osteosarcoma cells on the basis of H3K27ac signal intensity by ChIP-Seq and found that super-enhancer-associated genes contribute to the malignant potential of osteosarcoma. THZ2, a novel small molecular inhibitor, shows a powerful anti-osteosarcoma ability through suppress super-enhancer-associated genes selectively. Utilizing the characteristics of super-enhancers in cancer cells, we identified 5 critical super-enhancer-associated oncogenes. With the comparative and retrospective analysis in large numbers of human specimens from patients, these 5 oncogenes were observed closely related with patient prognosis. Our findings determined that targeting super-enhancer-associated oncogenes with transcriptional inhibitor, THZ2, was a promising therapeutic strategy in osteosarcoma, and provided novel candidate targets for patients with osteosarcoma.