dataset
posted on 2023-03-31, 21:43 authored by Jiajun Zhang, Weihai Liu, Changye Zou, Zhiqiang Zhao, Yuanying Lai, Zhi Shi, Xianbiao Xie, Gang Huang, Yongqian Wang, Xuelin Zhang, Zepei Fan, Qiao Su, Junqiang Yin, Jingnan Shen Super-enhancer analysis based on H3K27Ac ChIP-seq in U2-OS and SJSA-1 cells.
Funding
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
Science &Technology Planning Project of Guangzhou City
Sun Yat-sen University
Fundamental Research Funds for the Central Universities
Scientific Research 3 × 3 Project of Sun Yat-sen University
History
ARTICLE ABSTRACT
Malignancy of cancer cells depends on the active transcription of tumor-associated genes. Recently, unique clusters of transcriptional enhancers, termed super-enhancers, have been reported to drive the expression of genes that define cell identity. In this study, we characterized specific super-enhancer–associated genes of osteosarcoma, and explored their potential therapeutic value.
Super-enhancer regions were characterized through chromatin immunoprecipitation sequencing (ChIP-seq). RT-qPCR was used to detect the mRNA level of CDK7 in patient specimens and confirm the regulation of sensitive oncogenes by THZ2. The phosphorylation of the initiation-associated sites of RNA polymerase II (RNAPII) C-terminal repeat domain (CTD) was measured using Western blotting. Microarray expression analysis was conducted to explore transcriptional changes after THZ2 treatment. A variety of in vitro and in vivo assays were performed to assess the effects of CDK7 knockdown and THZ2 treatment in osteosarcoma.
Super-enhancers were associated with oncogenic transcripts and key genes encoding cell-type–specific transcription factors in osteosarcoma. Knockdown of transcription factor CDK7 reduced phosphorylation of the RNAPII CTD, and suppressed the growth and metastasis of osteosarcoma. A new specific CDK7 inhibitor, THZ2, suppressed cancer biology by inhibition of transcriptional activity. Compared with typical enhancers, osteosarcoma super-enhancer–associated oncogenes were particular vulnerable to this transcriptional disruption. THZ2 exhibited a powerful anti-osteosarcoma effect in vitro and in vivo.
Super-enhancer–associated genes contribute to the malignant potential of osteosarcoma, and selectively targeting super-enhancer–associated oncogenes with the specific CDK7 inhibitor THZ2 might be a promising therapeutic strategy for patients with osteosarcoma.
