The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway

Zhou, Luqian; Zhai, Mei; Huang, Yan; Xu, Sheng; An, Tao; Wang, Yunhong; Zhang, Rongcheng; Liu, Cui-Yun; Dong, Yanhan; Wang, Man; Qian, Lili; Ponnusamy, Murugavel; Zhang, Yuhui; Zhang, Jian; Wang, Kun

doi:10.1038/s41418-018-0206-4

Cited by 188 publications

(144 citation statements)

References 63 publications

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“…In addition to microRNAs (miRNAs), recent studies have found that circular RNAs (circRNAs) are involved in the pathological process of cardiovascular diseases such as atherosclerosis and myocardial ischemia/reperfusion injury . For example, Zhou et al found that circRNA ACR repressed autophagy and myocardial infarction by targeting Pink1‐mediated phosphorylation of FAM65B . Therefore, both circRNAs and miRNAs play important roles in the progression of diseases such as MI.…”

Section: Introductionmentioning

confidence: 99%

Circ_LAS1L regulates cardiac fibroblast activation, growth, and migration through miR‐125b/SFRP5 pathway

Sun

Zhao

et al. 2020

Cell Biochemistry & Function

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Funding informationThis work was supported by the young teachers program of Beijing university of Chinese medicine (2018-JYBZZ-JS094) and the scientific research project of Sichuan health committee (19PJ214).Current studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) are closely related in acute myocardial infarction (AMI). Previous studies have shown that miR-125b promotes fibrosis and up-regulates in cardiac fibroblasts (CFs), and further experiments showed that circ_LAS1L had multiple binding sites of miR-125b, and their expression was inversely related in AMI patients and CFs. RNA immunoprecipitation (RIP), pull down, and dual luciferase reporter gene assay all confirmed that miR-125b directly bound to circ_LAS1L. Circ_LAS1L overexpression promoted the expression of downstream target gene secreted frizzled-related protein 5 (SFRP5), inhibited the expression of alpha-SMA, collagen I, and collagen III, inhibited CF proliferation and migration, and promoted apoptosis. When cotransfected with circ_LAS1L overexpression vector and miR-125b mimics, the above gene expression and CF biological behaviours did not change significantly. But when cotransfected with circ_LAS1L overexpression vector and SFRP5 siRNA, SFRP5 expression was still down-regulated, the expression of alpha-SMA, collagen I, and collagen III was up-regulated, and the proliferation and migration of CFs were increased. Therefore, circ_LAS1L inhibits the activity of miR-125b by adsorbing it, thus promoting the expression of SFRP5 and then regulating the biological characteristics of CFs. These findings may provide an important experimental basis for the regulation of myocardial fibrosis after myocardial infarction.Significance of the study: Studies have shown that circular RNAs (circRNAs) play important roles in cardiovascular diseases, but there are few studies on their roles in the process of myocardial fibrosis. In this study, we found that circ_LAS1L was down-regulated in acute myocardial infarction (AMI) patients and cardiac fibroblasts (CFs), and could bind directly to miR-125b, thereby promoting the expression of downstream target gene secreted frizzled-related protein 5 (SFRP5), ultimately inhibiting the activation, proliferation and migration of CF, and promoting apoptosis. This suggests that circ_LAS1L/miR-125b/SFRP5 pathway can regulate the biological function of CF and may play an important role in the process of myocardial fibrosis, thus providing an important theoretical basis for the regulation of myocardial fibrosis after myocardial infarction. K E Y W O R D S cardiac fibroblast, circRNA, miR-125b, myocardial infarction, SFRP5 Li-ye Sun and Jin-chao Zhao contributed equally to this work.

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Section: Introductionmentioning

confidence: 99%

Circ_LAS1L regulates cardiac fibroblast activation, growth, and migration through miR‐125b/SFRP5 pathway

Sun

Zhao

et al. 2020

Cell Biochemistry & Function

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“…Despite multiple events, including inflammation, endoplasmic reticulum stress, autophagy, and intracellular Ca 2+ overload, have been reported to be involved in the pathogenesis of I/R injury, emerging evidences suggest that oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial I/R injury [4,5]. Mitochondria are the major source of reactive species oxygen (ROS) within the myocardium [6].…”

Section: Introductionmentioning

confidence: 99%

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

Meng

Jiao

Zhu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA (Hotair) was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of Hotair were exposed to I/R surgery. H9c2 cells were cultured and subjected to hypoxia/reoxygenation (H/R) stimulation to further verify the role and underlying mechanisms of Hotair in vitro. Histological examination, molecular detection, and functional parameters were determined in vivo and in vitro. In response to I/R or H/R treatment, Hotair expression was increased in a bromodomain-containing protein 4-dependent manner. Cardiac-restricted knockdown of Hotair exacerbated, whereas Hotair overexpression prevented I/R-induced oxidative stress, cardiac myocyte apoptosis, and cardiac dysfunction. Mechanistically, we observed that Hotair exerted its beneficial effects via activating AMP-activated protein kinase alpha (AMPKα). Further detection revealed that Hotair activated AMPKα through regulating the enhancer of zeste homolog 2/microRNA-451/calcium-binding protein 39 (EZH2/miR-451/Cab39) axis. We provide the evidence that endogenous lncRNA Hotair is an essential negative regulator for oxidative stress and cardiac myocyte apoptosis in myocardial I/R injury, which is dependent on AMPKα activation via the EZH2/miR-451/Cab39 axis.

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“…In addition, epigenetic changes in histones and genomes can affect alternative splicing, but also may cause a direct impact on the biological occurrence of circular RNA 19 . For example, a recent study showed that knockdown of DNMT3B altered the circular RNA expression, but was not related to changes in the linear host gene expression 20 . A recent study found that the transcription factor SOX9 can significantly upregulate the expression of hepatocellular carcinoma circFoxp1 21 .…”

Section: Discussionmentioning

confidence: 99%

A novel epigenetic regulation of circFoxp1 on Foxp1 in colon cancer cells

Luo

Liu

et al. 2020

Cell Death Dis

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Foxp1 is a tumor suppressor in colon cancer. However, circFoxp1 derived from Foxp1 is an oncogene. In this study, we aim to investigate the role of circFoxp1 in colon cancer and the regulatory mechanism between circFoxp1 and Foxp1. 78 human colon tumor tissues and the matched paracancerous tissues were collected. Quantitative polymerase chain reaction, immunohistochemistry, quantitative methylation-specific PCR, chromatin immunoprecipitation assay, CCK-8 assay, and Tumor xenograft in nude mice were performed. The expression of circFoxp1 was increased and Foxp1 was reduced in colon cancer tissues, which were associated with a poor overall survival rate of the patients with colon cancer. CircFoxp1 recruited DNMT1 to the promoter of Foxp1, leading to promotor hypermethylation, thereby inhibiting Foxp1 transcription. Interfering circFoxp1 by siRNA in SW620 cells significantly inhibited cell viability, while knockdown Foxp1 expression partially restored SW620 cell viability. In addition, knockdown of circFoxp1 significantly sensitized colon cancer cells to Capecitabine in vitro and vivo through regulating Foxp1. We discovered a novel epigenetic pathway that circFoxp1 regulated Foxp1 in colon cancer cells. CircFoxp1 may regulate DNA methylation and demethylation to coordinate colon cancer cell proliferation and participate in chemotherapy drug responses. Therefore, circFoxp1 may be a potential therapeutic target for colon cancer.

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The circular RNA ACR attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the Pink1/ FAM65B pathway

Cited by 188 publications

References 63 publications

Circ_LAS1L regulates cardiac fibroblast activation, growth, and migration through miR‐125b/SFRP5 pathway

Circ_LAS1L regulates cardiac fibroblast activation, growth, and migration through miR‐125b/SFRP5 pathway

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury

A novel epigenetic regulation of circFoxp1 on Foxp1 in colon cancer cells

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