Silencing long non-coding RNA MIAT ameliorates myocardial dysfunction induced by myocardial infarction via MIAT/miR-10a-5p/EGR2 axis

Abstract

Long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) has been widely-demonstrated to function as diagnostic markers for acute myocardial infarction (MI). This study was designed to explore the modulatory role of MIAT and its underlying molecular mechanism in MI. Firstly, MI mouse model was developed via ligation of the descending branch of the left coronary artery, and cell model was established through exposure to hypoxic conditions . Online prediction indicated that MIAT could bind to microRNA-10a-5p (miR-10a-5p), while miR-10a-5p was highlighted to bind to early growth response gene-2 (EGR2). MIAT and EGR2 were subsequently determined to be highly-expressed, whereas miR-10a-5p was found to be poorly-expressed in cardiomyocytes exposed to hypoxia as well as in MI mice using RT-qPCR and Western blot assay. The binding relationships between MIAT and miR-10a-5p, and between miR-10a-5p and EGR2 were further confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. The results of in vitro and in vivo experimentation also suggested that overexpression of miR-10a-5p or silencing of MIAT and EGR2 reduced cardiomyocyte apoptosis and increased ATP content, thus alleviating the impairment of cardiac function following MI. In a word, inhibition of MIAT protects against cardiac dysfunction induced by MI through the crosstalk with miR-10a-5p/EGR2.

LncRNA MIAT enhances cerebral ischaemia/reperfusion injury in rat model via interacting with EGLN2 and reduces its ubiquitin‐mediated degradation

“…It acts as a sponge for miR-1a in cardiomyocytes and exaggerates acute myocardial infarction via elevating the expression of early growth response gene-2 (EGR2). 21 Besides, it promotes p65 nuclear translocation and activates NF-kappaB signalling, resulting in elevated expression of cleaved-caspase-3 and Bax and downregulation of Bcl-2 in cardiomyocytes after I/R injury. 22 In cerebral microvascular endothelial cells, it sponges miR-204 and increases the expression of high mobility group box-1 protein (HMGB1), leading to enhanced cell apoptosis.…”

LncRNA MIAT promotes hypoxia‐induced H9C2 cell pyroptosis via binding to SF1 to inhibit CGRP transcription

“…Acute myocardial infarction/myocardial infarction presents with severe cardiomyocyte pyroptosis (Tibaut & Mekis, 2017). LncRNA MIAT acts as a crucial regulator in cardiomyocyte death and modulates the expression of other genes via binding to SF1 (Cao & Ma, 2021;Ip & Nakagawa, 2012). Moreover, CGRP targeted by SF1 splicing pre-mRNA plays an inhibitory role in cardiomyocyte death Zhou & Lou, 2008).…”

“…Previous research has demonstrated that lncRNA MIAT could act as a diagnostic marker for MI (Cao & Ma, 2021). To explore the regulatory mechanism of lncRNA MIAT in MI, H9C2 cells were subjected to hypoxia for 12 h to simulate MI in vitro.…”

“…Long non-coding RNAs (lncRNAs), generally non-coding RNAs with > 200 nucleotides, are involved in the physiological function of cardiomyocytes (Wang & Sun, 2020). Notably, lncRNA myocardial infarctionassociated transcript (lncRNA MIAT) is upregulated in MI and promotes cardiomyocyte apoptosis (Azat et al, 2019;Cao et al, 2021).…”

Identification and Interaction Analysis of Molecular Markers in Myocardial Infarction by Integrated Bioinformatics Analysis

“…PLA2G2A [61], CCL23 [62], CD53 [63], TREML4 [64], TREM2 [65], CD180 [66], HPSE (heparanase) [67], CELA2A [68], TNFRSF4 [69], AMBP (alpha-1-microglobulin/bikunin precursor) [70], SOX18 [71], PANX2 [72], RSPO2 [73], COMP (cartilage oligomeric matrix protein) [74], ASGR1 [75] and NOXA1 [76] are involved in progression of atherosclerosis. A previous study reported that S100A9 [77], ADORA3 [78], IL1R2 [79], FPR1 [80], CCL20 [81], CD163 [82], S100A8 [83], TLR2 [84], HAS2 [85], PTX3 [86], TIMP4 [87], AREG (amphiregulin) [88], LBP (lipopolysaccharide binding protein) [89], IL18R1 [90], ALOX5AP [91], RETN (resistin) [92], F13A1 [93], FPR2 [94], SAA1 [95], FLT3 [96], AQP4 [97], FCER1G [98], CCL18 [99], HP (haptoglobin) [100], CDK1 [101], SLC7A11 [102], CFTR (CF transmembrane conductance regulator) [103], F8 [104], STC1[44], IL18RAP [90], TIMP3 [105], PDE4D [106], CYP4A11 [107], SCN10A [108], APOB (apolipoprotein B) [109], ACE (angiotensin I converting enzyme) [110], PENK (proenkephalin) [111], HSPB6 [112], TLR9 [113], EGR1 [114], CACNG8 [115], FOXD3 [116], DBH (dopamine beta-hydroxylase) [117], FOXP3 [118], GLP1R [119], IL34 [120], CCN1 [121], ADRA2A [122], BGN (biglycan) [123], NOS2 [124], AGRN (agrin) [125], DRD1 [126], GNB3 [127], EGR2 [128], MDK (midkine) [129], NOTCH3 [130], AZIN2 [131], NOTCH1 [132], LOX...…”