CircBRD7通过其宿主基因的表观遗传学激活来减弱鼻咽癌的肿瘤生长和转移。

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancer Science Pub Date : 2023-11-08 DOI:10.1111/cas.15998
Jianxia Wei, Mengna Li, Shipeng Chen, Changning Xue, Lemei Zheng, Yumei Duan, Hongyu Deng, Songqing Fan, Wei Xiong, Ming Zhou
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引用次数: 0

摘要

BRD7被鉴定为鼻咽癌(NPC)的抑癌基因。环状RNA(CircRNA)作为致癌基因或肿瘤抑制剂参与NPC的发生和发展。然而,来源于BRD7的环状RNA形式在NPC中的功能和机制尚不清楚。在本研究中,我们首先确定circBRD7是一种从BRD7衍生的新型circRNA,它在体内抑制细胞增殖、迁移、侵袭NPC细胞以及异种移植物肿瘤的生长和转移。从机制上讲,circBRD7通过增强宿主基因BRD7启动子区组蛋白3赖氨酸27乙酰化(H3K27ac)的富集来促进BRD7的转录激活和表达,而BRD7促进了circBRD7的形成。因此,circBRD7与BRD7形成正反馈回路,抑制NPC的发展和进展。此外,BRD7表达的恢复挽救了circBRD7对NPC恶性进展的抑制作用。此外,circBRD7在NPC组织中表现出低表达,这与BRD7的表达呈正相关,与NPC患者的临床分期呈负相关。总之,circBRD7通过与其宿主基因BRD7形成正反馈环来减弱NPC的肿瘤生长和转移,靶向circBRD7/BRD7轴是NPC临床诊断和治疗的一种有前景的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

CircBRD7 attenuates tumor growth and metastasis in nasopharyngeal carcinoma via epigenetic activation of its host gene

CircBRD7 attenuates tumor growth and metastasis in nasopharyngeal carcinoma via epigenetic activation of its host gene

CircBRD7 attenuates tumor growth and metastasis in nasopharyngeal carcinoma via epigenetic activation of its host gene

BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNAs (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circular RNA forms derived from BRD7 in NPC are not well understood. In this study, we first identified that circBRD7 was a novel circRNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells, as well as the xenograft tumor growth and metastasis in vivo. Mechanistically, circBRD7 promoted the transcriptional activation and expression of BRD7 by enhancing the enrichment of histone 3 lysine 27 acetylation (H3K27ac) in the promoter region of its host gene BRD7, and BRD7 promoted the formation of circBRD7. Therefore, circBRD7 formed a positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the malignant progression of NPC. In addition, circBRD7 demonstrated low expression in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. Taken together, circBRD7 attenuates the tumor growth and metastasis of NPC by forming a positive feedback loop with its host gene BRD7, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC.

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来源期刊
Cancer Science
Cancer Science 医学-肿瘤学
自引率
3.50%
发文量
406
审稿时长
2 months
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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