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Circ_0000527通过调节miR-98-5p/XIAP通路促进视网膜母细胞瘤进展。

Circ_0000527 Promotes Retinoblastoma Progression through Modulating miR-98-5p/XIAP Pathway.

作者信息

Yu Binke, Zhao Jifei, Dong Yongxiao

机构信息

Department of Ophthalmology, Xianyang Hospital of Yan'an University, Xianyang, China.

Department of Ophthalmology, The First People's Hospital of Xianyang City, Xianyang, China.

出版信息

Curr Eye Res. 2021 Sep;46(9):1414-1423. doi: 10.1080/02713683.2021.1891255. Epub 2021 Feb 25.

Abstract

: Retinoblastoma (RB) is an intraocular malignancy that often occurs in childhood. Circular RNAs (circRNAs) play crucial roles in regulating the malignant phenotypes of various tumors. This study aimed to explore the role and potential mechanism of circ_0000527 in RB. The levels of circ_0000527, microRNA-98-5p (miR-98-5p) and X-linked inhibitor of apoptosis (XIAP) were determined by qRT-PCR or western blot. Cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays. Cell apoptosis, migration and invasion were evaluated by flow cytometry, transwell and scratch assays. Xenograft assay was conducted to analyze tumor growth . The binding relationship between miR-98-5p and circ_0000527 or XIAP was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ_0000527 and XIAP levels were increased, while miR-98-5p level was reduced in RB tissues and cells. Silencing of circ_0000527 suppressed the proliferation, migration and invasion of RB cells and promoted apoptosis. In addition, knockdown of circ_0000527 inhibited tumor growth in xenograft mice. Besides, circ_0000527 sponged miR-98-5p to regulate RB cell progression, and miR-98-5p targeted XIAP to mediate RB cell development. Moreover, circ_0000527 modulated XIAP expression via sequestering miR-98-5p. Circ_0000527 facilitated RB progression via regulating miR-98-5p/XIAP axis, which provided a promising therapeutic target for RB.

摘要

视网膜母细胞瘤(RB)是一种常发生于儿童期的眼内恶性肿瘤。环状RNA(circRNA)在调节各种肿瘤的恶性表型中起关键作用。本研究旨在探讨circ_0000527在RB中的作用及潜在机制。通过qRT-PCR或蛋白质免疫印迹法测定circ_0000527、微小RNA-98-5p(miR-98-5p)和X连锁凋亡抑制蛋白(XIAP)的水平。采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四氮唑溴盐(MTT)法和集落形成试验检测细胞增殖。通过流式细胞术、Transwell试验和划痕试验评估细胞凋亡、迁移和侵袭能力。进行异种移植试验以分析肿瘤生长情况。通过双荧光素酶报告基因和RNA免疫沉淀(RIP)试验验证miR-98-5p与circ_0000527或XIAP之间的结合关系。RB组织和细胞中circ_0000527和XIAP水平升高,而miR-98-5p水平降低。沉默circ_0000527可抑制RB细胞的增殖、迁移和侵袭,并促进细胞凋亡。此外,敲低circ_0000527可抑制异种移植小鼠的肿瘤生长。此外,circ_0000527通过海绵吸附miR-98-5p来调节RB细胞进程,且miR-98-5p靶向XIAP介导RB细胞发育。此外,circ_0000527通过隔离miR-98-5p来调节XIAP表达。circ_0000527通过调节miR-98-5p/XIAP轴促进RB进展,这为RB提供了一个有前景的治疗靶点。

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