The long noncoding RNA lncCIRBIL disrupts the nuclear translocation of Bclaf1 alleviating cardiac ischemia\u2013reperfusion injury

Yang Zhang,Benzhi Cai,Jin‐Ji Yang ,Xiaofang Zhang,Xuexin Jin,Ji-Qin Yang ,Yue Zhao,Yue Li,Qilong Han,Wenbo Ma,Yuan Jiang,Shang‐Xuan Li ,Yanjie Lu,Haiyu Gao,Ying Yang,Xiaoyu Fu,Hao Wu,Ying Liu ,Baofeng Yang,Tian Tian ,Genlong Xue,Zhenwei Pan

doi:10.1038/s41467-020-20844-3

Abstract

Cardiac ischemia–reperfusion (I/R) injury is a pathological process resulting in cardiomyocyte death. The present study aims to evaluate the role of the long noncoding RNA Cardiac Injury-Related Bclaf1-Inhibiting LncRNA (lncCIRBIL) on cardiac I/R injury and delineate its mechanism of action. The level of lncCIRBIL is reduced in I/R hearts. Cardiomyocyte-specific transgenic overexpression of lncCIRBIL reduces infarct area following I/R injury. Knockout of lncCIRBIL in mice exacerbates cardiac I/R injury. Qualitatively, the same results are observed in vitro. LncCIRBIL directly binds to BCL2-associated transcription factor 1 (Bclaf1), to inhibit its nuclear translocation. Cardiomyocyte-specific transgenic overexpression of Bclaf1 worsens, while partial knockout of Bclaf1 mitigates cardiac I/R injury. Meanwhile, partial knockout of Bclaf1 abrogates the detrimental effects of lncCIRBIL knockout on cardiac I/R injury. Collectively, the protective effect of lncCIRBIL on I/R injury is accomplished by inhibiting the nuclear translocation of Bclaf1. LncCIRBIL and Bclaf1 are potential therapeutic targets for ischemic cardiac disease.

Highlights

Cardiac ischemia–reperfusion (I/R) injury is a pathological process resulting in cardiomyocyte death
To screen for the Long noncoding RNAs (lncRNAs) involved in myocardial I/R injury, we performed lncRNA microarray analysis on cardiac tissues dissected from ischemia zone, border zone (BZ), and the remote non-ischemia zone (NIZ) of cardiac I/R mice
The data from NONCODE and UCSC database revealed that lncCIRBIL is an intergenic lncRNA of 862 nucleotides long and it locates on chromosome 6 (Supplementary Fig. 1)

Summary

Introduction

Cardiac ischemia–reperfusion (I/R) injury is a pathological process resulting in cardiomyocyte death. The present study aims to evaluate the role of the long noncoding RNA Cardiac Injury-Related Bclaf1-Inhibiting LncRNA (lncCIRBIL) on cardiac I/R injury and delineate its mechanism of action. LncCIRBIL directly binds to BCL2-associated transcription factor 1 (Bclaf1), to inhibit its nuclear translocation. LncCIRBIL and Bclaf[1] are potential therapeutic targets for ischemic cardiac disease. Long noncoding RNAs (lncRNAs) are a large and diverse class of RNAs that are >200 nucleotides in length and possesses no protein-coding property[4] They regulate diverse biological processes by altering gene expression networks in the nucleus and by modulating mRNA stability, translation, and protein function in the cytoplasm[5]. Our findings imply that lncCIRBIL and Bclaf[1] are potential therapeutic targets for ischemic cardiac disease

Methods

Results

Conclusion