SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition

Jia, Zhonghua; Wang, Jiaji; Shi, Qiong; Liu, Siyu; Wang, Weiping; Tian, Yuyao; Lu, Qiumin; Chen, Ping; Ma, Kangtao; Zhou, Chen

doi:10.1007/s10495-015-1201-6

Cited by 65 publications

(47 citation statements)

References 43 publications

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“…PDCD4 has been validated as a direct target of miR-21, and it has been reported that miR-21 could protect myocardium against ischemia-induced or H 2 O 2 -induced apoptosis and ischaemia/reperfusion injury through targeting PDCD4 [9, 32–33]. In this study, the luciferase report assay also validated that PDCD4 was a direct target of miR-499-5p because ectopic overexpression or inhibition of miR-499-5p increased or decreased the luciferase activities of cardiomyocytes transfected with the wild type PDCD4 3′UTR reporter vector rather than the mutant reporter vector, which is also validated by two recent researches [34–35]. Furthermore, the mRNA and protein expression of PDCD4 in cardiomyocytes is able to be modulated by miR-499-5p as detected by both gain-of-function and loss-of-function strategies.…”

Section: Discussionsupporting

confidence: 79%

MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4

Bao

et al. 2016

Oncotarget

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Recent studies have reported that miRNAs might play critical roles in acute myocardial infarction (AMI). The objective of this study is to investigate the role of miR-499-5p in AMI and its potential molecular mechanisms. The expression level of MiR-499-5p was remarkably decreased in the infarcted myocardial tissues and in the cultured neonatal rat cardiomyocytes induced by hypoxia. Overexpression or knockdown of miR-499-5p decreased or increased the apoptotic rates of cultured cardiomyocytes in vitro. In addition, ectopic overexpression of miR-499-5p in the rat AMI models with agomir reduced the myocardial infarct size through decreasing the cardiomyocytes apoptosis in the infarcted area of the rat hearts. PDCD4 (programmed cell death 4) was verified as a direct target of miR-499-5p by luciferase report assay, and ectopic overexpression or inhibition of miR-499-5p could inhibit or increase the PDCD4 expression at both the mRNA and protein levels. Furthermore, we found that ectopic overexpression of PDCD4 without miR-499-5p binding sites reversed miR-499-5p-mediated cardiomyocytes apoptosis. Together, these findings revealed the role of miR-499-5p in protecting the cardiomyocytes against apoptosis induced by AMI via its direct target PDCD4, which providing evidence for the miR-499-5p/PDCD4 pathway as a potential therapeutic target for patients with AMI.

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Section: Discussionsupporting

confidence: 79%

MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4

Bao

et al. 2016

Oncotarget

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“…This correlates with increased TNF-α production and NF-κB p65 phosphorylation [25]. Investigation of neonatal rat cardiomyocytes demonstrated that LPS inhibited the expression of miR-499, which in turn de-repressed SOX6 and PCDC4 leading to cardiomyocyte apoptosis through activation of the Bcl-2 family apoptotic pathway [111]. …”

Section: Discussionmentioning

confidence: 99%

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Chan

Wong

et al. 2016

Crit Care

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BackgroundSepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.MethodsWe searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool.ResultsObservational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common.ConclusionsAlthough non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

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“…Another high impact study was the investigation of LPS mediated cardiomyocyte apoptosis, which is a mechanism of sepsis-induced cardiac cell death. It was found that LPS stimulation inhibited microRNA (miR)-499 resulting in upregulated expression of the miR-499 target genes SOX6 and PDCD4 and activation of the Bcl-2 family pathway [3]. In a study by Yu et al the effect of melatonin in endoplasmatic reticulum stress was described [4].…”

Section: The Editors’ Choicementioning

confidence: 99%

Apoptosis on the move

Nowak-Śliwińska

2018

Apoptosis

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SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition

Cited by 65 publications

References 43 publications

MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4

MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4

The involvement of regulatory non-coding RNAs in sepsis: a systematic review

Apoptosis on the move

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