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超级增强子衍生的非编码 RNA 在人类癌症中的新兴作用。

The emerging role of super enhancer-derived noncoding RNAs in human cancer.

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

出版信息

Theranostics. 2020 Sep 2;10(24):11049-11062. doi: 10.7150/thno.49168. eCollection 2020.

Abstract

Super enhancers (SEs) are large clusters of adjacent enhancers that drive the expression of genes which regulate cellular identity; SE regions can be enriched with a high density of transcription factors, co-factors, and enhancer-associated epigenetic modifications. Through enhanced activation of their target genes, SEs play an important role in various diseases and conditions, including cancer. Recent studies have shown that SEs not only activate the transcriptional expression of coding genes to directly regulate biological functions, but also drive the transcriptional expression of non-coding RNAs (ncRNAs) to indirectly regulate biological functions. SE-derived ncRNAs play critical roles in tumorigenesis, including malignant proliferation, metastasis, drug resistance, and inflammatory response. Moreover, the abnormal expression of SE-derived ncRNAs is closely related to the clinical and pathological characterization of tumors. In this review, we summarize the functions and roles of SE-derived ncRNAs in tumorigenesis and discuss their prospective applications in tumor therapy. A deeper understanding of the potential mechanism underlying the action of SE-derived ncRNAs in tumorigenesis may provide new strategies for the early diagnosis of tumors and targeted therapy.

摘要

超级增强子 (SEs) 是一组相邻的增强子的大型簇,它们驱动调节细胞身份的基因的表达; SE 区域可以富集大量转录因子、共因子和增强子相关的表观遗传修饰。通过增强其靶基因的激活,SEs 在包括癌症在内的各种疾病和状况中发挥重要作用。最近的研究表明,SEs 不仅激活编码基因的转录表达以直接调节生物功能,而且还驱动非编码 RNA (ncRNA) 的转录表达以间接调节生物功能。SE 衍生的 ncRNA 在肿瘤发生中发挥关键作用,包括恶性增殖、转移、耐药性和炎症反应。此外,SE 衍生的 ncRNA 的异常表达与肿瘤的临床和病理特征密切相关。在这篇综述中,我们总结了 SE 衍生的 ncRNA 在肿瘤发生中的功能和作用,并讨论了它们在肿瘤治疗中的潜在应用。更深入地了解 SE 衍生的 ncRNA 在肿瘤发生中的作用的潜在机制可能为肿瘤的早期诊断和靶向治疗提供新的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e20/7532672/0a91d8ac02cc/thnov10p11049g001.jpg

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