MiR-200a-3p Aggravates DOX-Induced Cardiotoxicity by Targeting PEG3 Through SIRT1/NF-κB Signal Pathway
Doxorubicin (DOX) is a widely used cytotoxic drug whose application is limited by its severe side effects. Little was known regarding how to offset its side effects. Therefore this study aims to explore the role of miR-200a-3p in DOX-induced cardiotoxicity and its possible mechanism. DOX-induced myocardial injury rat models were established, which were then injected with miR-200a-3p inhibitor (miR-200a-3p suppression) to observe the effects of miR-200a-3p on cell proliferation, and apoptosis. Heart function and weights of rat models were also measured. Cardiomyocytes were induced by DOX, in which PEG3 knockdown or corresponding plasmids were transfected to assess the possible effect of PEG3 on cell activity. Dual luciferase reporter assay was applied to verify the binding of PEG3 with miR-200a-3p. Elevated levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and left ventricular end-diastolic pressure (LVEDP), as well as suppressed left ventricular systolic pressure (LVSP) and ± dp/dt max were showed in myocardial injury rat models. DOX induced myocardial injury and increased miR-200a-3p expression levels. miR-200a-3p inhibitor could partially attenuate DOX-induced cardiotoxicity in rat models, while PEG3 could regulate myocardial injury in DOX-treated cell models. miR-200a-3p, by targeting PEG3 through SIRT1/NF-κB signal pathway, regulated cell proliferation, inflammation and apoptosis of myocardiocytes. The results in current study demonstrated that miR-200a-3p regulates cell proliferation and apoptosis of cardiomyocytes by targeting PEG3 through SIRT1/NF-κB signal pathway. This result may provide a potential clue for the treatment of DOX-induced cardiotoxicity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Cardiovascular toxicology - 21(2021), 4 vom: 05. Apr., Seite 302-313 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Fu, Qinghua [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 10.12.2021 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s12012-020-09620-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM321966856 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM321966856 | ||
| 003 | DE-627 | ||
| 005 | 20240229152805.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12012-020-09620-3 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1306.xml |
| 035 | |a (DE-627)NLM321966856 | ||
| 035 | |a (NLM)33638775 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Fu, Qinghua |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MiR-200a-3p Aggravates DOX-Induced Cardiotoxicity by Targeting PEG3 Through SIRT1/NF-κB Signal Pathway |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.12.2021 | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Doxorubicin (DOX) is a widely used cytotoxic drug whose application is limited by its severe side effects. Little was known regarding how to offset its side effects. Therefore this study aims to explore the role of miR-200a-3p in DOX-induced cardiotoxicity and its possible mechanism. DOX-induced myocardial injury rat models were established, which were then injected with miR-200a-3p inhibitor (miR-200a-3p suppression) to observe the effects of miR-200a-3p on cell proliferation, and apoptosis. Heart function and weights of rat models were also measured. Cardiomyocytes were induced by DOX, in which PEG3 knockdown or corresponding plasmids were transfected to assess the possible effect of PEG3 on cell activity. Dual luciferase reporter assay was applied to verify the binding of PEG3 with miR-200a-3p. Elevated levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and left ventricular end-diastolic pressure (LVEDP), as well as suppressed left ventricular systolic pressure (LVSP) and ± dp/dt max were showed in myocardial injury rat models. DOX induced myocardial injury and increased miR-200a-3p expression levels. miR-200a-3p inhibitor could partially attenuate DOX-induced cardiotoxicity in rat models, while PEG3 could regulate myocardial injury in DOX-treated cell models. miR-200a-3p, by targeting PEG3 through SIRT1/NF-κB signal pathway, regulated cell proliferation, inflammation and apoptosis of myocardiocytes. The results in current study demonstrated that miR-200a-3p regulates cell proliferation and apoptosis of cardiomyocytes by targeting PEG3 through SIRT1/NF-κB signal pathway. This result may provide a potential clue for the treatment of DOX-induced cardiotoxicity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Doxorubicin-induced myocardial injury | |
| 650 | 4 | |a NF-κB | |
| 650 | 4 | |a PEG3 | |
| 650 | 4 | |a Proliferation | |
| 650 | 4 | |a SIRT1 | |
| 650 | 4 | |a miR-200a-3p | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Kruppel-Like Transcription Factors |2 NLM | |
| 650 | 7 | |a MIRN200 microRNA, rat |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Peg3 protein, rat |2 NLM | |
| 650 | 7 | |a Doxorubicin |2 NLM | |
| 650 | 7 | |a 80168379AG |2 NLM | |
| 650 | 7 | |a Sirt1 protein, rat |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 650 | 7 | |a Sirtuin 1 |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 700 | 1 | |a Pan, Hongwei |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Rong, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Zhaofen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cardiovascular toxicology |d 2001 |g 21(2021), 4 vom: 05. Apr., Seite 302-313 |w (DE-627)NLM120494043 |x 1559-0259 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2021 |g number:4 |g day:05 |g month:04 |g pages:302-313 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12012-020-09620-3 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2021 |e 4 |b 05 |c 04 |h 302-313 | ||