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结直肠癌中的超级增强子和新的治疗靶点。

Super-enhancers and novel therapeutic targets in colorectal cancer.

机构信息

Department of Pathology & Pathophysiology, and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Cell Death Dis. 2022 Mar 11;13(3):228. doi: 10.1038/s41419-022-04673-4.

Abstract

Transcription factors, cofactors, chromatin regulators, and transcription apparatuses interact with transcriptional regulatory elements, including promoters, enhancers, and super-enhancers (SEs), to coordinately regulate the transcription of target genes and thereby control cell behaviors. Among these transcriptional regulatory components and related elements, SEs often play a central role in determining cell identity and tumor initiation and progression. Therefore, oncogenic SEs, which are generated within cancer cells in oncogenes and other genes important in tumor pathogenesis, have emerged as attractive targets for novel cancer therapeutic strategies in recent years. Herein, we review the identification, formation and activation modes, and regulatory mechanisms for downstream genes and pathways of oncogenic SEs. We also review the therapeutic strategies and compounds targeting oncogenic SEs in colorectal cancer and other malignancies.

摘要

转录因子、辅助因子、染色质调节剂和转录装置与转录调控元件相互作用,包括启动子、增强子和超级增强子 (SEs),共同调节靶基因的转录,从而控制细胞行为。在这些转录调控成分和相关元件中,SEs 通常在决定细胞身份以及肿瘤起始和进展中起核心作用。因此,近年来,在致癌基因和肿瘤发病机制中其他重要基因内产生的致癌 SEs 已成为新型癌症治疗策略的有吸引力的靶标。在此,我们综述了致癌 SEs 的鉴定、形成和激活模式以及下游基因和通路的调控机制。我们还综述了针对结直肠癌和其他恶性肿瘤中的致癌 SEs 的治疗策略和化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2aa/8917125/e4e657f21353/41419_2022_4673_Fig1_HTML.jpg

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