降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡

毕沈艳; 陈灵寒; 喻溥蛟; 王佳琪; 王丽君; 许嘉鸿

doi:10.12066/j.issn.1007-2861.2720

上海大学学报(自然科学版) >

2026 , Vol. 32 >Issue 2: 202 - 211

DOI: https://doi.org/10.12066/j.issn.1007-2861.2720

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降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡

毕沈艳 ,
陈灵寒 ,
喻溥蛟 ,
王佳琪 ,
王丽君 ,
许嘉鸿

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1. 宁夏医科大学上海市浦东新区公利医院研究生培养基地, 上海 200135;
2. 上海大学生命科学学院, 上海 200444;
3. 上海市浦东新区公利医院心血管内科, 上海 200135

收稿日期: 2025-12-08

网络出版日期: 2026-05-11

基金资助

国家自然科学基金资助项目(82370370, 82400349); 浦东新区卫生健康委员会优秀青年医学人才培养计划资助项目(PWRq-2024-25); 上海市卫生健康系统重点学科资助项目(2024ZDXK0024); 浦东新区卫健委重点学科资助项目(PWZxk2022-15)

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Alleviation of cardiomyocyte apoptosis by reducing RNA binding protein FUS and inhibiting circ-ZNF609

BI Shenyan ,
CHEN Linghan ,
YU Pujiao ,
WANG Jiaqi ,
WANG Lijun ,
XU Jiahong

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1. Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai 200135, China;
2. School of Life Sciences, Shanghai University, Shanghai 200444, China;
3. Department of Cardiology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, China

Received date: 2025-12-08

Online published: 2026-05-11

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摘要

探究RNA结合蛋白(RNA binding protein,RBP)肉瘤融合(fused in sarcoma,FUS)蛋白调控circ-ZNF609(circBase ID:mmu_circ_0001797)减轻由心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)导致的心肌细胞凋亡.基于生物信息学分析发现,FUS是circ-ZNF609两翼反向互补序列结合的潜在剪接因子.构建I/RI动物模型和氧糖剥夺/恢复(oxygen-glucose deprivation/recovery,OGD/R)细胞模型,通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling,TUNEL)法染色、实时定量逆转录多聚酶链反应(quantitativereverse transcription polymerase chain reaction,qRT-PCR)等方法证明了FUS能调控心肌细胞circ-ZNF609的生物生成,抑制FUS对OGD/R诱导的心肌细胞凋亡的保护作用被circ-ZNF609过表达所逆转.因此,抑制FUS是对抗心肌缺血再灌注损伤病理过程的一种有前景的治疗策略.

关键词： 肉瘤融合(fused in sarcoma, FUS); 环状RNA; circ-ZNF609; 心肌细胞凋亡

本文引用格式

毕沈艳 , 陈灵寒 , 喻溥蛟 , 王佳琪 , 王丽君 , 许嘉鸿 . 降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡[J]. 上海大学学报(自然科学版), 2026 , 32(2) : 202 -211 . DOI: 10.12066/j.issn.1007-2861.2720

Abstract

This paper aims to investigate the regulatory role of RNA binding protein (RBP) fused in sarcoma (FUS) in the mechanism by which circ-ZNF609 (circBase ID: mmu_circ_0001797) alleviates cardiomyocyte apoptosis caused by ischemia/reperfusion injury (I/RI). Bioinformatics analysis revealed that FUS was a potential splicing factor binding to the flanking reverse complementary sequences of circ-ZNF609. Subsequently, an I/RI animal model and an oxygen-glucose deprivation/recovery (OGD/R) cell model were constructed. Methods such as terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to validate that FUS can regulate the biogenesis of circ-ZNF609 in myocardial cells. The protective effect of FUS on OGD/R-induced cardiomyocyte apoptosis is reversed by circ-ZNF609 overexpression. Therefore, inhibiting FUS is a promising therapeutic strategy against the pathological process of myocardial ischemia/reperfusion injury.

Key words： fused in sarcoma (FUS); circular RNA; circ-ZNF609; cardiomyocyte apoptosis

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