microRNA-223 promotes autophagy to aggravate lung ischemia-reperfusion injury by inhibiting the expression of transcription factor HIF2α

Lung ischemia-reperfusion (I/R) injury severely endangers human health, and recent studies have suggested that certain microRNAs (miRNAs) play important roles in this pathological phenomenon. The current study aimed to ascertain the ability of miR-223 to influence lung I/R injury by targeting hypoxia-inducible factor-2α (HIF2α). First, mouse models of lung I/R injury were established: during surgical procedures, pulmonary arteries and veins and unilateral pulmonary portal vessels were blocked and resuming bilateral pulmonary ventilation, followed by restoration of bipulmonary ventilation. In addition, a lung I/R injury cell model was constructed by exposure to hypoxic reoxygenation (H/R) in mouse pulmonary microvascular endothelial cells (PMVECs). Expression of miR-223, HIF2α, and β-catenin in tissues or cells was determined by RT-qPCR and Western blot analysis. Correlation between miR-223 and HIF2α was analyzed by dual luciferase reporter gene assay. Furthermore, lung tissue injury and mouse PMVEC apoptosis was evaluated by hematoxylin and eosin (H&E), TUNEL staining, and flow cytometry. Autophagosomes in cells were detected by light chain 3 immunofluorescence assay. miR-223 was expressed at a high level while HIF2α/β-catenin was downregulated in tissues and cells with lung I/R injury. Furthermore, miR-223 targeted and repressed HIF2α expression to downregulate β-catenin expression. The miR-223/HIF2α/β-catenin axis aggravated H/R injury in mouse PMVECs and lung I/R injury in mice by enhancing autophagy. Taken together, miR-223 inhibits HIF2α to repress β-catenin, thus contributing to autophagy to complicate lung I/R injury. These findings provide a promising therapeutic target for treating lung I/R injury.

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Abstract 13141: Cellular Microrna 449b Upregulation Sensitizes Ischemia/reperfusion Injury via Inhibition of Nrf-1, Increasing Ros Production and Apoptosis in the Diabetic Heart

Circulation ◽

10.1161/circ.132.suppl_3.13141 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Hang Wang ◽

Wayne Lau ◽

Erhe Gao ◽

Walter Koch ◽

Xin Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Experimental Studies ◽

Diabetic Heart ◽

Luciferase Reporter ◽

Proteomics Data ◽

Luciferase Reporter Gene ◽

Gene Assay

Myocardial ischemic/reperfusion (MI/R) injury is significantly enhanced in diabetes by incompletely understood mechanisms. Recent clinical and experimental studies demonstrate that hypoadiponectinemia during diabetes enhances oxidative stress and exaggerates MI/R injury. However, molecular mechanisms responsible for hypoadiponectinemia-induced oxidative stress remain unknown. In a discovery-driven fashion, we determined the role of cardiac microRNAs in the MI/R response in adiponectin knockout (APNKO) mice. From 68 total miRNAs differentially expressed between APNKO and wild type (WT) mice, miRNA 449b was identified as the microRNA most relevant to oxidative stress and apoptosis. In cultured neonatal cardiomyocytes, miRNA 449b silencing inhibited hypoxia/reoxygenation-induced apoptosis, whereas miR-449b overexpression significantly increased oxidative stress and cardiomyocyte apoptosis. In APNKO mice, administration of anti-miR-449b decreased oxidative stress (-17.2±3.8%, p<0.05), reduced caspase-3 activity (-21.3±4.2%, p<0.05), attenuated myocardial apoptosis (-16.3±4.1%, p<0.05), and improved myocardial function (1.4±0.3 fold). To identify the downstream molecule regulated by miRNA 449b, we integrated transcriptomics and proteomics data with computational annotation data, and identified Nrf-1 as a miRNA 449b target. A luciferase reporter gene assay demonstrated that miRNA 449b inhibited Nrf-1 expression via Nrf-1 mRNA 3’UTR region binding. Finally, we demonstrated that miRNA 449b was significantly upregulated, Nrf-1 expression was significantly decreased, and the anti-oxidative molecule metallothionein (MT) was significantly inhibited in the diabetic heart subjected to MI/R. Administration of anti-miR-449b in diabetic animals upregulated Nrf-1 and MT expression, reduced oxidative stress, and improved cardiac function (P<0.01) after MI/R. Taken together, this study provides the first evidence that hypoadiponectinemia during diabetes causes cardiac miRNA-449b upregulation and subsequent downregulation of Nrf-1 and MT, thus enhancing oxidative stress and MI/R injury. MicroRNA 449b may represent a potential therapeutic target against diabetic heart disease.

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Mir10a overexpression aggravates the renal ischemia-reperfusion injury associated with a decrease in PIK3CA

10.21203/rs.2.23453/v2 ◽

2020 ◽

Author(s):

Dongsheng Xu ◽

Wenjun Li ◽

Tao Zhang ◽

Gang Wang

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Luciferase Reporter ◽

Akt Pathway ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

Underlying Mechanisms ◽

Related Proteins ◽

Hypoxia Reoxygenation

Abstract Background: To investigate the effect of miR-10a on the renal tissues with ischemia-reperfusion (I/R) injury in rats and explore the underlying mechanisms of miR-10a in the HK-2 cells of hypoxia-reoxygenation. Methods: The miR-10a level was measured in renal tissues with I/R rats by RT-PCR. In order to research the role of miR-10a in the renal tissues, miR-10 agonist and miR-10a antagonist were used to treat I/R rats. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in serum, renal histopathology, apoptosis of cells in renal tissues were analyzed, separately. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blot. The HK-2 cell was cultured to study the mechanism of miR-10a in the model of hypoxia-reoxygenation. The dual luciferase reporter gene assay was used to confirm the PI3K p100 catalytic subunit α (PIK3CA) was a target gene of miR-10a. Results: After renal I/R injury in rats, the miR-10a expression was significantly increased (p<0.05). Injection of miR-10a agonist significantly aggravated the injury of renal and raised the apoptosis of cells in renal in rats with renal I/R injury (p<0.05). However, administration of miR-10a antagonist obviously improved the injury of renal, decreased the renal cells apoptosis and inhibited the PI3K/Akt pathway activity (p<0.05). In vitro experiments, the negative relation between PIK3CA and miR-10a was confirmed. Further, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased the cells apoptosis via up-regulating PI3K/Akt pathway (p<0.05). Conclusion: miR-10a could aggravate the renal I/R injury associated with a decrease in PIK3CA/PI3K/Akt pathway.

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microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01742-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yong Li ◽

Hongbo Zhang ◽

Zhanhu Li ◽

Xiaoju Yan ◽

Yuan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Mouse Models ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Luciferase Reporter ◽

Gene Assay ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

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Up-regulation of miR-499a-5p decreases cerebral ischemia/reperfusion injury by targeting PDCD4

10.21203/rs.3.rs-297082/v1 ◽

2021 ◽

Author(s):

Weifeng Shan ◽

Huifeng Ge ◽

Bingquan Chen ◽

Linger Huang ◽

Shaojun Zhu ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Ischemia Reperfusion Injury ◽

Cell Model ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Artery Occlusion ◽

Tunel Staining ◽

Cerebral Ischemia Reperfusion

Abstract MiR-499a-5p was significantly down-regulated in degenerative tissues and correlated with apoptosis. Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found the plasma levels of miR-499a-5p were significantly down-regulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay and flow cytometry analysis. These findings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.

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Contribution of microRNA-30d to the prevention of the thyroid cancer progression: mechanism and implications

10.21203/rs.3.rs-25018/v1 ◽

2020 ◽

Author(s):

Yuan Shao ◽

Shaoqiang Zhang ◽

Xiaoxia Wang ◽

Xin Sun ◽

Jie Wu ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Progression ◽

Endocrine Tumor ◽

Luciferase Reporter ◽

Tunel Staining ◽

Loss Of Function ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

Low Expression

Abstract Background Thyroid cancer is a major endocrine tumor and represents an emerging health problem worldwide. MicroRNAs (miRNAs) have been addressed to be associated with the pathogenesis and progression of thyroid cancer. However, it remains largely unknown what functions miR-30d may exert on thyroid cancer. This study herein aimed to identify the functional significance and mechanism of miR-30d in the progression of thyroid cancer. Methods The expression of miR-30d and ubiquitin-specific protease 22 (USP22) in cancerous tissues of patients with thyroid cancer was measured using RT-qPCR and Western blot analysis. In response to the gain- or loss-of-function of miR-30d and USP22, cell apoptosis was evaluated by flow cytometry and TUNEL staining in combination with the measurement of apoptosis-related proteins. The interactions among miR-30d, USP22, SIRT1, FOXO3a and PUMA were explored using a series of assays, including dual-luciferase reporter gene assay, Co-IP and ChIP assay. The effects of miR-30d and USP22 on thyroid tumorigenesis were finally validated in vivo. Results MiR-30b presented aberrant low expression in thyroid cancer tissues and this low expression correlated with poor prognosis of thyroid cancer patients. miR-30d promoted apoptosis of thyroid cancer cells through targeting USP22, an up-regulated gene in thyroid cancer. USP22 could enhance the stability of SIRT1 by inducing deubiquitination which consequently contributed to FOXO3a deacetylation-induced PUMA repression. It was verified that this regulatory mechanism was responsible for the pro-apoptotic effect of miR-30d by the in vivo tumorigenicity assay. Conclusion To conclude, the progression of thyroid cancer can be suppressed by miR-30d-mediated inhibition of USP22, provides a promising therapeutic target for thyroid cancer treatment.

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Long noncoding RNA-MEG3 contributes to myocardial ischemia–reperfusion injury through suppression of miR-7-5p expression

Bioscience Reports ◽

10.1042/bsr20190210 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 2

Author(s):

Liyuan Zou ◽

Xiaokun Ma ◽

Shuo Lin ◽

Bingyuan Wu ◽

Yang Chen ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Caspase 3 ◽

Ischemia Reperfusion Injury ◽

Cell Model ◽

Ischemia Reperfusion ◽

Luciferase Reporter

Abstract Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) plays an important role in protection of ischemia–reperfusion (I/R) injury in brain and liver. However, role of MEG3 in myocardial I/R injury remains unclear. Here, the role of MEG3 in protection of myocardial I/R injury and its association with microRNA-7-5p (miR-7-5p) was investigated using rat cardiac I/R model and myocardial I/R cell model. Our results showed that MEG3 was significantly up-regulated and miR-7-5p was significantly down-regulated after I/R. Following I/R, the levels of intact PARP and intact caspase-3 were reduced, while the cleaved fragments of PARP and caspase-3 were increased. TUNEL assay showed an increase in cardiomyocyte apoptosis after I/R. The levels of I/R-induced creatine kinase (CK) and lactate dehydrogenase (LDH) were inhibited by knockdown of MEG3 (siMEG3). SiMEG3 increased cell proliferation and inhibited cell apoptosis after I/R. In contrast, overexpression of MEG3 increased the I/R-induced CK and LDH activities and cell apoptosis and decreased cell proliferation. The dual-luciferase reporter system showed a direct binding of MEG3 to miR-7-5p. The level of miR-7-5p was negatively associated with the change in levels of MEG3 in H9c2 cells. The levels of intact RARP1 and caspase-3 were significantly increased by knockdown of MEG3. Co-transfection of miR-7-5p inhibitor with siMEG3 activates CK and LDH, significantly decreased cell proliferation, increased cell apoptosis, and decreased intact poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3. In summary, down-regulation of MEG3 protects myocardial cells against I/R-induced apoptosis through miR-7-5p/PARP1 pathway, which might provide a new therapeutic target for treatment of myocardial I/R injury.

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Rno-microRNA-30c-5p promotes myocardial ischemia reperfusion injury in rats through activating NF-κB pathway and targeting SIRT1

10.21203/rs.2.15405/v5 ◽

2020 ◽

Author(s):

Jianfeng Chen ◽

Mingming Zhang ◽

Shouyan Zhang ◽

Junlong Wu ◽

Shufeng Xue

Keyword(s):

Myocardial Ischemia ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Sirtuin 1 ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Tunel Staining ◽

Myocardial Cells ◽

Myocardial Ischemia Reperfusion

Abstract Background: This study aimed to investigate the regulatory effect of rno-microRNA-30c-5p (rno-miR-30c-5p) on myocardial ischemia reperfusion (IR) injury in rats and the underlying molecular mechanisms.Methods: A rat model of myocardial IR injury was established. The infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. The pathologic changes of myocardial tissues were detected by hematoxylin-eosin staining. The apoptosis of myocardial cells was measured by TUNEL staining and flow cytometry. The mRNA expression of rno-miR-30c-5p and Sirtuin 1 (SIRT1) was detected by quantitative real-time PCR. The levels of IL-1β, IL-6 and TNF-α were detected by enzyme linked immunosorbent assay. The protein expression of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 was detected by Western blot. The interaction between rno-miR-30c-5p and SIRT1 was predicted by TargetScan, and further identified by dual luciferase reporter gene and RNA immunoprecipitation assay.Results: The myocardial IR injury model was successfully established in rats. IR induced the myocardial injury in rats and increased the expression of rno-miR-30c-5p. Overexpression of rno-miR-30c-5p enhanced the inflammation, promoted the apoptosis, and activated NF-κB pathway in IR myocardial cells. SIRT1 was the target gene of rno-miR-30c-5p. Silencing of SIRT1 reversed the effects of rno-miR-30c-5p inhibitor on the apoptosis and NF-κB pathway in IR myocardial cells.Conclusions: Rno-miR-30c-5p promoted the myocardial IR injury in rats through activating NF-κB pathway and down-regulating SIRT1.

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Targeting ZFP64/GAL-1 axis promotes therapeutic effect of nab-paclitaxel and reverses immunosuppressive microenvironment in gastric cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02224-x ◽

2022 ◽

Vol 41 (1) ◽

Author(s):

Mengxuan Zhu ◽

Pengfei Zhang ◽

Shan Yu ◽

Cheng Tang ◽

Yan Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Zinc Finger Protein ◽

Tumor Formation ◽

Humanized Mice ◽

Luciferase Reporter ◽

Tunel Staining ◽

Luciferase Reporter Gene ◽

Paclitaxel Resistance ◽

Gene Assay ◽

Immunosuppressive Microenvironment

Abstract Background Chemoresistance is a main obstacle in gastric cancer (GC) treatment, but its molecular mechanism still needs to be elucidated. Here, we aim to reveal the underlying mechanisms of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resistance in GC. Methods We performed RNA sequencing (RNA-seq) on samples from patients who were resistant or sensitive to nab-paclitaxel, and identified Zinc Finger Protein 64 (ZFP64) as critical for nab-paclitaxel resistance in GC. CCK8, flow cytometry, TUNEL staining, sphere formation assays were performed to investigate the effects of ZFP64 in vitro, while subcutaneous tumor formation models were established in nude mice or humanized mice to evaluate the biological roles of ZFP64 in vivo. Chromatin immunoprecipitation sequencing (CHIP-seq) and double-luciferase reporter gene assay were conducted to reveal the underlying mechanism of ZFP64. Results ZFP64 overexpression was linked with aggressive phenotypes, nab-paclitaxel resistance and served as an independent prognostic factor in GC. As a transcription factor, ZFP64 directly binds to Galectin-1 (GAL-1) promoter and promoted GAL-1 transcription, thus inducing stem-cell like phenotypes and immunosuppressive microenvironment in GC. Importantly, compared to treatment with nab-paclitaxel alone, nab-paclitaxel plus GAL-1 blockade significantly enhanced the anti-tumor effect in mouse models, particularly in humanized mice. Conclusions Our data support a pivotal role for ZFP64 in GC progression by simultaneously promoting cellular chemotherapy resistance and tumor immunosuppression. Treatment with the combination of nab-paclitaxel and a GAL-1 inhibitor might benefit a subgroup of GC patients.

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MicroRNA-203a-3p Regulates the Apoptosis of MPP+ Induced SH-SY5Y Cells by Targeting A-Synuclein

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2320 ◽

2020 ◽

Vol 10 (6) ◽

pp. 838-844

Author(s):

Jianxin Jiang ◽

Ran Xiong ◽

Jun Lu ◽

Xiaolin Wang ◽

Xiaobo Gu

Keyword(s):

Cell Model ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Pcr Assay ◽

Luciferase Reporter Gene Assay ◽

Gene Assay ◽

Enhanced Expression ◽

Direct Binding ◽

Induced Apoptosis

Parkinson's disease (PD) is a universal central nervous system degenerative diseases and has a serious impact on people's lives. MicroRNA-203a-3p (miR-203a-3p) is a tumor-inhibiting factor. Nevertheless, the role and mechanism of miR-203a-3p in PD remain unclear. Therefore, this investigated the role and underlying mechanism of miR-203a-3p in PD. Firstly, we have established a PD cell model by treating SH-SY5Y cells with MMP+. We found that cell viability gradually decreased with increased MMP+ concentration. Subsequently, we choose 2000 μM MMP+ for subsequent experiments. Then, qRT-PCR assay demonstrated that miR-203a-3p was down-regulated in MMP+ treated SH-SY5Y cells. Next, results from TargetScan and dual luciferase reporter gene assay suggested that a-synuclein (SNCA), an important genetic risk factor of PD, had direct binding sites with miR-203a-3p. Subsequently, we confirmed that miR-203a-3p negatively regulated SNCA expression in SH-SY5Y cells. Finally, we investigated the influence of miR-203a-3p on MMP+ -induced SH-SY5Y cells. CCK-8 assay results showed that MMP + reduced cell proliferation and induced apoptosis were inhibited by miR-203a-3p up-regulation. In addition, we found that MMP+ enhanced expression of SNCA, p53 and cleaved Caspase-3 proteins was reduced by miR-203a-3p overexpression. However, these changes were reversed by SNCA-plasmid. In conclusion, miR-203a-3p regulated the apoptosis of MPP+ induced SH-SY5Y cells by targeting SNCA. miR-203a-3p/SNCA axis might be a new latent targets for PD therapy.

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LncRNA Gm4419 induces cell apoptosis in hepatic ischemia–reperfusion injury via regulating the miR-455–SOX6 axis

Biochemistry and Cell Biology ◽

10.1139/bcb-2019-0331 ◽

2020 ◽

Vol 98 (4) ◽

pp. 474-483 ◽

Cited By ~ 3

Author(s):

Dongjian Ying ◽

Xinhua Zhou ◽

Yi Ruan ◽

Luoluo Wang ◽

Xiang Wu

Keyword(s):

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Cell Model ◽

Ischemia Reperfusion ◽

Annexin V ◽

Luciferase Reporter ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion

Long non-coding RNA (lncRNA) is known to be involved in a variety of diseases. However, the role of Gm4419 in hepatic ischemia–reperfusion (I/R) injury remains unknown. To study this, we first established a rat model of hepatic I/R, and a BRL-3A cell model of hypoxia–reoxygenation (H/R) for in vivo and in vitro studies. Staining with hematoxylin and eosin and hepatic injury scores were used to evaluate the degree of hepatic I/R injury. Cell apoptosis was assessed via staining with Edu, and with annexin V–FITC–propidium iodide assays. The interactions between Gm4419 and miR-455, as well as miR-455 and SOX6 were evaluated via luciferase reporter activity assays and RNA immunoprecipitation assays. In vivo, we found that Gm4419 was up-regulated in the rats subjected to I/R. Moreover, knockdown of Gm4419 alleviated the I/R-induced liver damage in the rats. In vitro, knockdown of Gm4419 alleviated H/R-induced apoptosis in BRL-3A cells. Interestingly, we found that miR-455 is a target of Gm4419, and Gm4419 regulates the expression of miR-455 via sponging. Furthermore, SOX6 was proven to be the target of miR-455. Finally, rescue experiments confirmed that knockdown of Gm4419 inhibits apoptosis by regulating miR-455 and SOX6 in H/R-treated BRL-3A cells. Therefore, our findings show that the lncRNA Gm4419 accelerates hepatic I/R injury by targeting the miR-455–SOX6 axis, which suggests a novel therapeutic target for hepatic I/R injury.

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