<i>MiR-138</i> protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1

Zhu, Hang; Xue, Hao; Jin, Qinhua; Guo, Juan; Chen, Yundai

doi:10.1042/bsr20170296

Cited by 18 publications

(15 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 The cardioprotective effects of miR-138 have been well-studied, 17,18,25 suggesting the important role of miR-138 in regulating cardiomyocytes death. 17 The cardioprotective effects of miR-138 have been well-studied, 17,18,25 suggesting the important role of miR-138 in regulating cardiomyocytes death.…”

Section: Mir-138 Was a Downstream Target Of Lncrna-letmentioning

confidence: 99%

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

Zhang

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Ischemic heart disease (IHD) is a common cardiovascular disease, occurs when coronary artery blood circularity cannot match with the heart's need. The present work attempted to study the effects of long noncoding RNA (lncRNA) low expression in tumor (LET) on the progression of IHD. H9c2 cells were injured by hypoxia to mimic a cell model of IHD. The effects of lncRNA‐LET on hypoxia‐injured H9c2 cells were tested by using cell counting kit‐8 assay, flow cytometry, and Western blot analysis. MicroRNA‐138 (miR‐138) expression was tested by a quantitative real‐time polymerase chain reaction, and the expression of c‐Jun N‐terminal kinase (JNK) and p38MAPK (p38–mitogen‐activated protein kinase) proteins was measured by Western blot analysis. We found that hypoxia exposure significantly repressed the viability of H9c2 cells, and induced apoptosis. Meanwhile, phosphorylation of JNK and p38MAPK was enhanced by hypoxia. The expression of lncRNA‐LET was repressed by hypoxia. Overexpression of lncRNA‐LET attenuated hypoxia‐induced injury in H9c2 cells. Moreover, miR‐138 was a downstream effector of lncRNA‐LET, that miR‐138 was highly expressed in lncRNA‐LET‐overexpressed cell. The cardioprotective effects of lncRNA‐LET were abolished when miR‐138 was silenced. In conclusion, this study revealed the cardioprotective function of lncRNA‐LET. lncRNA‐LET conferred its cardioprotective effects possibly via upregulation of miR‐138 and thus repressing the JNK and p38MAPK pathways.

show abstract

Section: Mir-138 Was a Downstream Target Of Lncrna-letmentioning

confidence: 99%

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

Zhang

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Hypoxia-inducible apoptosis is a condition in which a low oxygen concentration induces the overexpression of HIF-1; this initializes apoptotic conditions by inducing high concentrations of BNIP3 and causing stabilization of p53 [ 92 , 93 , 94 ]. MiR-138 exhibits a protective effect against hypoxia-induced apoptosis via the MLK3/JNK/c-jun pathway [ 95 ]. By downregulating JNK, p38, Bax, and Caspase-3 levels, and upregulating Bcl-2 , we can find an apoptotic for miR-320, namely IGF-1.…”

Section: Mirnas In Cardiovascular Diseasesmentioning

confidence: 99%

A MicroRNA Perspective on Cardiovascular Development and Diseases: An Update

Islas

Moreno-Cuevas

2018

IJMS

View full text Add to dashboard Cite

In this review, we summarize the latest research pertaining to MicroRNAs (miRs) related to cardiovascular diseases. In today’s molecular age, the key clinical aspects of diagnosing and treating these type of diseases are crucial, and miRs play an important role. Therefore, we have made a thorough analysis discussing the most important candidate protagonists of many pathways relating to such conditions as atherosclerosis, heart failure, myocardial infarction, and congenital heart disorders. We approach miRs initially from the fundamental molecular aspects and look at their role in developmental pathways, as well as regulatory mechanisms dysregulated under specific cardiovascular conditions. By doing so, we can better understand their functional roles. Next, we look at therapeutic aspects, including delivery and inhibition techniques. We conclude that a personal approach for treatment is paramount, and so understanding miRs is strategic for cardiovascular health.

show abstract

“…Even though the deleterious effects of miR-138-5p downregulation in the damaged CNS are explored here for the first time, the cytoprotective properties of this miRNA are well documented in astrocytes injured under ischemic conditions [56], glioblastoma [57], glioma stem cells [25], as well as in neural stem cells [58], pulmonary artery smooth muscle cells [59] and cardiomyocytes under hypoxia [60,61], and in microglial cells exposed to oxidative levels of H2O2 [62]. According to these studies, cytoprotection by miR-138-5p relies on its targeting and inhibition of the cell death-related genes Casp3, BLCAP and MXD1 [25], LCN2 [56,63], BIM [57], Mst-1 [64], and Mlk3 [61,62], or even in the inhibition of the JNK and p38MAPK pathways [58].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-138-5p targets pro-apoptotic factors and favours neural cell survival

Maza

Silvan

Muñoz‐Galdeano

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The central nervous system-enriched microRNA miR-138-5p becomes significantly downregulated after spinal cord injury (SCI). miR-138-5p modulates essential biological processes in the Central Nervous System (CNS). It also overcomes apoptosis by inhibiting the expression of proteins, including the effector CASP3, key in different cell death pathways. Therefore, we hypothesize that miR-138-5p downregulation following SCI underlies the overexpression of apoptotic genes and sensitizes neural cells to noxious stimuli. To confirm this hypothesis, this study aims a) to identify and validate miR-138-5p targets among the pro-apoptotic genes overexpressed following SCI; and b) to confirm that the miR-138-5p is able to modulate cell death in neural cells Methods We employed computational tools to identify potential pro-apoptotic targets of miR-138-5p. Dysregulation of selected targets after SCI and its relationship to changes in miR-138-5p expression were analysed through qRT-PCR in a rat SCI model. Validation of the regulation of those apoptotic targets was carried out by luciferase reporter, qRT-PCR, and immunoblot assays in cultures of neural cell lines transfected with a mimetic of the microRNA. The functional effects of modifying the expression of miR-138-5p were later examined in cultures of the rat neural cell line C6 employing enzymatic assays to measure the activity of effector CASP3 and CASP7 together with MTT and flow cytometry assays to estimate cell death. Results Consensus among different algorithms identified 209 potential targets of miR-138-5p. A total of 176 of them become dysregulated after SCI, including proteins basic to apoptosis process such as CASP3 and CASP7, or BAK (Bcl-2 homologous antagonist/killer). Downregulation of miR-138-5p after SCI correlates with the overexpression of these three targets. Cell culture analyses confirm that miR-138-5p targets their 3’UTRs and reduces their expression after microRNA transfection. Transfection of miR-138-5p in C6 cell line results in a reduced effector caspase activity and protects cells from apoptotic stimulation. Conclusions Our results demonstrate that downregulation of miR-138-5p after SCI can be deleterious to spinal neural cells. A mixture of direct effects mediated by the upregulation of apoptotic targets and indirect effects related to the upregulation of cell cycle proteins can be expected.

show abstract

MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1

Cited by 18 publications

References 22 publications

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

Retracted: LncRNA‐LET relieves hypoxia‐induced injury in H9c2 cells through regulation of miR‐138

A MicroRNA Perspective on Cardiovascular Development and Diseases: An Update

MicroRNA-138-5p targets pro-apoptotic factors and favours neural cell survival

Contact Info

Product

Resources

About