Metformin Protects against H2O2-Induced Cardiomyocyte Injury by Inhibiting the miR-1a-3p/GRP94 Pathway.

Abstract:

:Ischemia-reperfusion (I/R) injury is a major side effect of the reperfusion treatment of the ischemic heart. Few therapies are available for the effective prevention of this injury caused by the oxidative stress-induced cardiomyocyte apoptosis. Metformin was shown to have a potential cardiac protective effect and ability to reduce cardiac events, but the exact mechanism remains unclear. Here, we aimed to confirm and investigate the mechanisms underlying potential metformin activity against I/R injury in response to oxidative stress. We determined that the expression of miR-1a-3p was significantly increased in neonatal rat ventricular cells (NRVCs), which were exposed to H2O2in vitro and in the hearts of mice that underwent the I/R injury. MiR-1a-3p was shown to target the 3' UTR of GRP94, which results in the accumulation of un- or misfolded proteins, leading to the endoplasmic reticulum (ER) stress. The obtained results demonstrated that C/EBP β directly induces the upregulation of miR-1a-3p by binding to its promoter. Furthermore, as a direct allosteric AMPK activator, metformin was shown to activate AMPK and significantly reduce C/EBP β and miR-1a-3p levels compared with those in the control group. In conclusion, metformin protects cardiomyocytes against H2O2 damage through the AMPK/C/EBP β/miR-1a-3p/GRP94 pathway, which indicates that metformin may be applied for the treatment of I/R injury.

journal_name

Mol Ther Nucleic Acids

authors

Zhang Y,Liu X,Zhang L,Li X,Zhou Z,Jiao L,Shao Y,Li M,Leng B,Zhou Y,Liu T,Liu Q,Shan H,Du Z

doi

10.1016/j.omtn.2018.09.001

subject

Has Abstract

pub_date

2018-12-07 00:00:00

pages

189-197

issn

2162-2531

pii

S2162-2531(18)30240-3

journal_volume

13

pub_type

杂志文章
  • METTL14 Gene Polymorphisms Confer Neuroblastoma Susceptibility: An Eight-Center Case-Control Study.

    abstract::Neuroblastoma is the primary cause of cancer death in childhood. METTL14 is tightly linked to cancer. However, whether single-nucleotide polymorphisms (SNPs) in the METTL14 gene could predispose to neuroblastoma susceptibility lacks evidence. With an epidemiology case-control study, associations between METTL14 gene S...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.08.009

    authors: Zhuo Z,Lu H,Zhu J,Hua RX,Li Y,Yang Z,Zhang J,Cheng J,Zhou H,Li S,Li L,Xia H,He J

    更新日期:2020-08-14 00:00:00

  • Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma.

    abstract::Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are deeply involved in the development of various cancers. This study identified that SBF2-AS1, an early-stage-specific lncRNA, is critical for the tumorigenesis of lung adenocarcinoma (LUAD). We first analyzed LUAD transcriptome data from The Cancer G...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.04.004

    authors: Chen R,Xia W,Wang S,Xu Y,Ma Z,Xu W,Zhang E,Wang J,Fang T,Zhang Q,Dong G,Cho WC,Ma PC,Brandi G,Tavolari S,Ujhazy P,Metro G,Popper HH,Yin R,Qiu M,Xu L

    更新日期:2019-06-07 00:00:00

  • N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool.

    abstract::MicroRNAs (miRNAs or miRs) play crucial roles in biological and pathological processes. Some miRNAs also appear as promising biomarkers and therapeutic tools. However, the epitranscriptomic regulation of miRNAs is not yet fully elucidated in all of their fields of application. We report that adenosine methylation of m...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.08.010

    authors: Briand J,Sérandour AA,Nadaradjane A,Bougras-Cartron G,Heymann D,Ory B,Vallette FM,Cartron PF

    更新日期:2020-08-14 00:00:00

  • In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9.

    abstract::The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo selection strategy to identify RNA aptamers (targeting motifs)...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.27

    authors: Mi J,Ray P,Liu J,Kuan CT,Xu J,Hsu D,Sullenger BA,White RR,Clary BM

    更新日期:2016-04-26 00:00:00

  • The lncRNA Plscr4 Controls Cardiac Hypertrophy by Regulating miR-214.

    abstract::Cardiac hypertrophy accompanied by maladaptive cardiac remodeling is the uppermost risk factor for the development of heart failure. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have various biological functions, and their vital role in the regulation of cardiac hypertrophy still needs to be explored. In this...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2017.12.018

    authors: Lv L,Li T,Li X,Xu C,Liu Q,Jiang H,Li Y,Liu Y,Yan H,Huang Q,Zhou Y,Zhang M,Shan H,Liang H

    更新日期:2018-03-02 00:00:00

  • Time-Restricted PiggyBac DNA Transposition by Transposase Protein Delivery Using Lentivirus-Derived Nanoparticles.

    abstract::Continuous innovation of revolutionizing genome engineering technologies calls for an intensified focus on new delivery technologies that not only match the inventiveness of genome editors but also enable the combination of potent delivery and time-restricted action of genome-modifying bits and tools. We have previous...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.02.006

    authors: Skipper KA,Nielsen MG,Andersen S,Ryø LB,Bak RO,Mikkelsen JG

    更新日期:2018-06-01 00:00:00

  • Mbd2 Mediates Retinal Cell Apoptosis by Targeting the lncRNA Mbd2-AL1/miR-188-3p/Traf3 Axis in Ischemia/Reperfusion Injury.

    abstract::Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells (RGCs) and Mbd2 kno...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.01.011

    authors: Ge Y,Zhang R,Feng Y,Li H

    更新日期:2020-03-06 00:00:00

  • Identification of Novel Tumor-Microenvironment-Regulating Factor That Facilitates Tumor Immune Infiltration in Colon Cancer.

    abstract::Colon cancer is one of the most common malignancies causing death worldwide. It is well known that the cells of the tumor microenvironment contribute to the progression and prognosis of colon cancer. However, the gene alterations and potential remodeling mechanisms in the tumor microenvironment of colon cancer remain ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.08.029

    authors: Wang Y,Wang Y,Xu C,Liu Y,Huang Z

    更新日期:2020-08-29 00:00:00

  • Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into Pancreas Cancer.

    abstract::Gemcitabine has been considered a first-line chemotherapy agent for the treatment of pancreatic cancer. However, the initial response rate of gemcitabine is low and chemoresistance occurs frequently. Aptamers can be effectively internalized into cancer cells via binding to target molecules with high affinity and speci...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.06.003

    authors: Park JY,Cho YL,Chae JR,Moon SH,Cho WG,Choi YJ,Lee SJ,Kang WJ

    更新日期:2018-09-07 00:00:00

  • Lipidoid Nanoparticles Containing PD-L1 siRNA Delivered In Vivo Enter Kupffer Cells and Enhance NK and CD8(+) T Cell-mediated Hepatic Antiviral Immunity.

    abstract::Effective clinical application of antiviral immunotherapies necessitates enhancing the functional state of natural killer (NK) and CD8(+) T cells. An important mechanism for the establishment of viral persistence in the liver is the activation of the PD-1/PD-L1 inhibitory pathway. To examine the role of hepatic myeloi...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2012.63

    authors: Dolina JS,Sung SS,Novobrantseva TI,Nguyen TM,Hahn YS

    更新日期:2013-02-19 00:00:00

  • Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies.

    abstract::Analysis of the tissue distribution of plasmid DNA after administration of nonviral gene delivery systems is best accomplished using quantitative real-time polymerase chain reaction (qPCR), although published strategies do not allow determination of the absolute mass of plasmid delivered to different tissues. Generall...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.79

    authors: Ho JK,White PJ,Pouton CW

    更新日期:2016-10-04 00:00:00

  • Preclinical in vivo evaluation of the safety of a multi-shRNA-based gene therapy against HIV-1.

    abstract::Highly active antiretroviral therapy (HAART) has significantly improved the quality of life and the life expectancy of HIV-infected individuals. Still, drug-induced side effects and emergence of drug-resistant viral variants remain important issues that justify the exploration of alternative therapeutic options. One s...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2013.48

    authors: Centlivre M,Legrand N,Klamer S,Liu YP,Jasmijn von Eije K,Bohne M,Rijnstra ES,Weijer K,Blom B,Voermans C,Spits H,Berkhout B

    更新日期:2013-09-03 00:00:00

  • H19 Increases IL-17A/IL-23 Releases via Regulating VDR by Interacting with miR675-5p/miR22-5p in Ankylosing Spondylitis.

    abstract::Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.11.025

    authors: Zhang X,Ji S,Cai G,Pan Z,Han R,Yuan Y,Xu S,Yang J,Hu X,Chen M,Wu M,Ma Y,Deng J,Gao X,Guan S,Xu S,Shuai Z,Laslett L,Pan F

    更新日期:2020-03-06 00:00:00

  • MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis.

    abstract::Apoptosis and calcification of endplate chondrocytes (EPCs) can exacerbate intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes (MSC-exosomes) are reported to have the therapeutic potential in IVDD. However, the effects and related mechanisms of MSC-exosomes on EPCs are still unclear. We aim...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.09.026

    authors: Xie L,Chen Z,Liu M,Huang W,Zou F,Ma X,Tao J,Guo J,Xia X,Lyu F,Wang H,Zheng C,Jiang J

    更新日期:2020-09-26 00:00:00

  • E-selectin Targeting PEGylated-thioaptamer Prevents Breast Cancer Metastases.

    abstract::E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.103

    authors: Morita Y,Kamal M,Kang SA,Zhang R,Lokesh GL,Thiviyanathan V,Hasan N,Woo S,Zhao D,Leslie M,Suh S,Razaq W,Rui H,Gorenstein DG,Volk DE,Tanaka T

    更新日期:2016-12-13 00:00:00

  • Menin Coordinates C/EBPβ-Mediated TGF-β Signaling for Epithelial-Mesenchymal Transition and Growth Inhibition in Pancreatic Cancer.

    abstract::Menin displays either tumor suppression or promotion functions in a context-dependent manner. Previously, we proposed that Menin acts as a tumor suppressor by inhibiting cell growth in pancreatic ductal adenocarcinoma (PDAC), whereas the relationship between the Menin expression and overall survival rate of PDAC patie...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.08.013

    authors: Cheng P,Chen Y,He TL,Wang C,Guo SW,Hu H,Ni CM,Jin G,Zhang YJ

    更新日期:2019-12-06 00:00:00

  • The MicroRNA Biology of the Mammalian Nucleus.

    abstract::MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that are primarily considered to be post-transcriptional negative regulators of gene expression acting in the cytoplasm. Over a decade of research has focused on this canonical paradigm of miRNA function, with many success stories. Indeed, miRNAs have been id...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2014.40

    authors: Roberts TC

    更新日期:2014-08-19 00:00:00

  • Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease.

    abstract::Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made to...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2015.33

    authors: Parsi S,Smith PY,Goupil C,Dorval V,Hébert SS

    更新日期:2015-10-06 00:00:00

  • Lipid Nanoparticle-mediated siRNA Transfer Against PCTAIRE1/PCTK1/Cdk16 Inhibits In Vivo Cancer Growth.

    abstract::PCTAIRE1/CDK16/PCTK1 plays critical roles in cancer cell proliferation and antiapoptosis. To advance our previously published in vitro results with PCTAIRE1 silencing, we examined the in vivo therapeutic potential of this approach by using small interfering RNA (siRNA) encapsulated by lipid nanoparticles. Therapy expe...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.40

    authors: Yanagi T,Tachikawa K,Wilkie-Grantham R,Hishiki A,Nagai K,Toyonaga E,Chivukula P,Matsuzawa S

    更新日期:2016-06-28 00:00:00

  • MicroRNA199a-Based Post-transcriptional Detargeting of Gene Vectors for Hepatocellular Carcinoma.

    abstract::A gene therapeutic platform needs to be both efficient and safe. The criterion of safety is particularly important for diseases like hepatocellular carcinoma (HCC), which develop in a background of an already compromised liver. Gene vectors can be constructed either by targeting HCC or by detargeting liver and/or othe...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.08.016

    authors: Dhungel B,Ramlogan-Steel CA,Layton CJ,Steel JC

    更新日期:2018-12-07 00:00:00

  • Aptamer-Targeted Plasmonic Photothermal Therapy of Cancer.

    abstract::Novel nanoscale bioconjugates combining unique plasmonic photothermal properties of gold nanoparticles (AuNPs) with targeted delivery using cell-specific DNA aptamers have a tremendous potential for medical diagnostics and therapy of many cell-based diseases. In this study, we demonstrate the high anti-cancer activity...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2017.08.007

    authors: Kolovskaya OS,Zamay TN,Belyanina IV,Karlova E,Garanzha I,Aleksandrovsky AS,Kirichenko A,Dubynina AV,Sokolov AE,Zamay GS,Glazyrin YE,Zamay S,Ivanchenko T,Chanchikova N,Tokarev N,Shepelevich N,Ozerskaya A,Badrin E,Belug

    更新日期:2017-12-15 00:00:00

  • Specific inhibition of SRC kinase impairs malignant glioma growth in vitro and in vivo.

    abstract::Malignant glioma is a severe cancer with a poor prognosis. Local occurrence and rare metastases of malignant glioma make it a suitable target for gene therapy. Several studies have demonstrated the importance of Src kinase in different cancers. However, these studies have focused mainly on Src-deficient mice or pharma...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2012.13

    authors: Stedt H,Alasaarela L,Samaranayake H,Pikkarainen J,Määttä AM,Kholová I,Parker AS,Ylä-Herttuala S

    更新日期:2012-05-01 00:00:00

  • Endogenous MicroRNA Competition as a Mechanism of shRNA-Induced Cardiotoxicity.

    abstract::Gene knockdown using short hairpin RNAs (shRNAs) is a promising strategy for targeting dominant mutations; however, delivering too much shRNA can disrupt the processing of endogenous microRNAs (miRNAs) and lead to toxicity. Here, we sought to understand the effect that excessive shRNAs have on muscle miRNAs by treatin...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.12.007

    authors: Course MM,Gudsnuk K,Desai N,Chamberlain JR,Valdmanis PN

    更新日期:2020-03-06 00:00:00

  • miR-1266 Contributes to Pancreatic Cancer Progression and Chemoresistance by the STAT3 and NF-κB Signaling Pathways.

    abstract::Pancreatic cancer is characterized by chemoresistance after several cycles of chemotherapy, which is a major issue responsible for treatment failure of pancreatic cancer. Therefore, it is necessary to explore the specific mechanism underlying chemotherapeutic resistance to overcome this issue. Here we report that miR-...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.01.004

    authors: Zhang X,Ren D,Wu X,Lin X,Ye L,Lin C,Wu S,Zhu J,Peng X,Song L

    更新日期:2018-06-01 00:00:00

  • Double-target Antisense U1snRNAs Correct Mis-splicing Due to c.639+861C>T and c.639+919G>A GLA Deep Intronic Mutations.

    abstract::Fabry disease is a rare X-linked lysosomal storage disorder caused by deficiency of the α-galactosidase A (α-Gal A) enzyme, which is encoded by the GLA gene. GLA transcription in humans produces a major mRNA encoding α-Gal A and a minor mRNA of unknown function, which retains a 57-nucleotide-long cryptic exon between ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.88

    authors: Ferri L,Covello G,Caciotti A,Guerrini R,Denti MA,Morrone A

    更新日期:2016-10-25 00:00:00

  • Transcriptional Factor Yin Yang 1 Promotes the Stemness of Breast Cancer Cells by Suppressing miR-873-5p Transcriptional Activity.

    abstract::Transcription factor Yin Yang 1 (YY1) is upregulated in multiple tumors and plays essential roles in tumor proliferation and metastasis. However, the function of YY1 in breast cancer stemness remains unclear. Herein, we found that YY1 expression was negatively correlated with the overall survival and relapse-free surv...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.06.018

    authors: Guo Q,Wang T,Yang Y,Gao L,Zhao Q,Zhang W,Xi T,Zheng L

    更新日期:2020-09-04 00:00:00

  • A Hyperactive Transposase Promotes Persistent Gene Transfer of a piggyBac DNA Transposon.

    abstract::Nonviral vector systems are used increasingly in gene targeting and gene transfer applications. The piggyBac transposon represents an alternative integrating vector for in vivo gene transfer. We hypothesized that this system could achieve persistent gene transfer to the liver when administered systemically. We report ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2012.12

    authors: Burnight ER,Staber JM,Korsakov P,Li X,Brett BT,Scheetz TE,Craig NL,McCray PB Jr

    更新日期:2012-10-16 00:00:00

  • Targeting RNA-Mediated Toxicity in C9orf72 ALS and/or FTD by RNAi-Based Gene Therapy.

    abstract::A hexanucleotide GGGGCC expansion in intron 1 of chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The corresponding repeat-containing sense and antisense transcripts cause a gain of toxicity through the accumulation o...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.02.001

    authors: Martier R,Liefhebber JM,García-Osta A,Miniarikova J,Cuadrado-Tejedor M,Espelosin M,Ursua S,Petry H,van Deventer SJ,Evers MM,Konstantinova P

    更新日期:2019-06-07 00:00:00

  • Implications of Newly Identified Brain eQTL Genes and Their Interactors in Schizophrenia.

    abstract::Schizophrenia (SCZ) is a devastating genetic mental disorder. Identification of the SCZ risk genes in brains is helpful to understand this disease. Thus, we first used the minimum Redundancy-Maximum Relevance (mRMR) approach to integrate the genome-wide sequence analysis results on SCZ and the expression quantitative ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.05.026

    authors: Cai L,Huang T,Su J,Zhang X,Chen W,Zhang F,He L,Chou KC

    更新日期:2018-09-07 00:00:00

  • ube3d, a New Gene Associated with Age-Related Macular Degeneration, Induces Functional Changes in Both In Vivo and In Vitro Studies.

    abstract::Neovascular age-related macular degeneration (AMD) is characterized by the formation of choroidal neovascularization, which is responsible for more than 80% of cases of severe vision loss. Ubiquitin protein ligase E3D (UBE3D) gene missense has been proven to be associated with neovascular AMD in the East Asian populat...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2020.02.010

    authors: Xia H,Zhang Q,Shen Y,Bai Y,Ma X,Zhang B,Qi Y,Zhang J,Hu Q,Du W,Zhu L,Zhou P,Wang B,Xu H,Huang L,Li X

    更新日期:2020-06-05 00:00:00