Evidence map›Paper›PMID 29304479›Full record

ArticleRedox biology2018

MicroRNA-140-5p aggravates doxorubicin-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2.

Lisha Zhao, Yan Qi, Lina Xu, Xufeng Tao, Xu Han, Lianhong Yin, Jinyong Peng

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 184 papers.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed
12.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

184 citing papers in PubMed, 345 citations in OpenAlex.

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124 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Lisha ZhaoCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Yan QiCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Lina XuCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Xufeng TaoCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Xu HanCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Lianhong YinCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
Jinyong PengCollege of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: jinyongpeng2014@163.com.
Dalian Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px. Total of 18 differentially expressed microRNAs in rat heart tissue caused by DOX were screened out using microRNA microarray assay, especially showing that miR-140-5p was significantly increased by DOX which was selected as the target miRNA. Double-luciferase reporter assay showed that miR-140-5p directly targeted Nrf2 and Sirt2, as a result of affecting the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a, and thereby increasing DOX-caused myocardial oxidative damage. In addition, the levels of intracellular ROS were significantly increased or decreased in H9C2 cells treated with DOX after miR-140-5p mimic or miR-140-5p inhibitor transfection, respectively, as well as the changed expression levels of Nrf2 and Sirt2. Furthermore, DOX- induced myocardial oxidative damage was worsened in mice treated with miR-140-5p agomir, and however the injury was alleviated in the mice administrated with miR-140-5p antagomir. Therefore, miR-140-5p plays an important role in DOX-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2. Our data provide novel insights for investigating DOX-induced heart injury. In addition, miR-140-5p/ Nrf2 and miR-140-5p/Sirt2 may be the new targets to treat DOX-induced cardiotoxicity.

Indexed as

AnimalsCardiotoxicityCell LineCell SurvivalDoxorubicinGene Expression RegulationHeart InjuriesHumansMicroRNAsMyocardiumMyocytes, CardiacNeoplasmsNF-E2-Related Factor 2Oxidative StressRatsSirtuin 2DoxorubicinMicroRNAsMIRN140 microRNA, ratNfe2l2 protein, ratNF-E2-Related Factor 2Sirt2 protein, ratSirtuin 2CardiotoxicityDoxorubicinmiR-140-5pNrf2Oxidative damageSirt2

Identifiers

PMID29304479
PMCPMC5975069
OpenAlexW2778620777

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.