Long noncoding RNA MAPKAPK5-AS1 promoted lipopolysaccharide-induced inflammatory damage in the myocardium by sponging microRNA-124-3p/E2F3

Abstract

Background Myocardial dysfunction caused by sepsis (SIMD) leads to high mortality in critically ill patients. We investigated the function and mechanism of long non-coding RNA MAPKAPK5-AS1 (lncRNA MAPKAPK-AS1) on lipopolysaccharide (LPS)-induced inflammation response in vivo and in vitro. Method Male SD rats were utilized for in vivo experiments. Rat cardiomyocytes (H9C2) were employed for in vitro experiments. Western blotting was employed to measure protein expression, and RT-PCR was performed to measure mRNA expression of inflammation factors. TUNEL and flow cytometry were carried out to evulate cell apoptosis. Result The results showed that the expression of MAPKAPK5-AS1 was increased, while the expression of miR-124-3p was decreased in the inflammatory damage induced by LPS in vivo and in vitro. Knockdown of MAPKAPK5-AS1 reduced LPS-induced cell apoptosis and inflammation response, while overexpression of miR-124-3p weakened the effects of MAPKAPK5-AS1 knockdown on LPS-induced cell apoptosis and inflammation response. Moreover, miR-124-3p was identified as a downstream miRNA of MAPKAPK5-AS1, and E2F3 was a target of miR-214-3p. MAPKAPK5-AS1 knockdown increased the expression of miR-124-3p, while miR-124-3p overexpression reduced the expression of MAPKAPK5-AS1. In addition, miR-124-3p was found to downregulate E2F3 expression in H9C2 cells. Conclusion MAPKAPK5-AS1/miR-124-3p/E2F3 axis regulates LPS-related H9C2 cell apoptosis and inflammatory response.

Propofol synergizes with circAPBB2 to protect against hypoxia/reoxygenation‐induced oxidative stress, inflammation, and apoptosis of human cardiomyocytes

“…Myocardial infarction is defined as cardiomyocyte cell death and its progression involves the regulation of noncoding RNAs such as long noncoding RNAs, miRNAs and circRNAs 19–22 . Dill et al have reported that the imprinted Dlk1‐Dio3 genomic region that contains a noncoding RNA cluster and regulates cardiac homeostasis has the potential as a therapeutic target for CVDs 23 .…”

“…Myocardial infarction is defined as cardiomyocyte cell death and its progression involves the regulation of noncoding RNAs such as long noncoding RNAs, miRNAs and circRNAs. [19][20][21][22] Dill et al have reported that the imprinted Dlk1-Dio3 genomic region that contains a noncoding RNA cluster and regulates cardiac homeostasis has the potential as a therapeutic target for CVDs. 23 Convincing evidence has indicated the contribution of circRNAs to cardiac inflammation, cardiac fibrosis, cardiac regeneration, autophagy, apoptosis, and oxidative stress signaling during myocardial infarction.…”

Xinyang tablet ameliorates sepsis-induced myocardial dysfunction by regulating Beclin-1 to mediate macrophage autophagy and M2 polarization through LncSICRNT1 targeting E3 ubiquitin ligase TRAF6

“…Grouping: The mice were grouped randomly as follows (N = 12): (1) control group: injected intraperitoneally with 10 mg/kg normal saline at one time, with other treatments the same as the LPS group; (2) LPS group; (3) LPS + oe-LncSICRNT1 group: immediately injected with oe-LncSICRNT1 adeno-associated virus plasmids (19 × 10 7 TU/per mouse) via tail veins after modeling [ 40 ]; (4) LPS + oe-negative control (NC) group: immediately injected with an equivalent amount of oe-NC plasmids via tail veins after modeling; (5) LPS + XYT-L, M, and H group (the mice were intragastrically administered with low-, medium-, and high-dose XYT on day 2 after modeling); (6) LPS + digoxin group (positive drug control group); (7) LPS + XYT-M + si-LncSICRNT1 group: immediately injected with si-LncSICRNT1 plasmids (19 × 10 7 TU/per mouse) via tail veins and treated with medium-dose XYT suspension 2 days later after modeling; (8) LPS + XYT-M + si-NC group: immediately injected with equivalent amounts of si-NC plasmids and treated with medium-dose XYT suspension on the second day after modeling. All plasmids were provided by GenePharma (Shanghai, China).…”

Revealing Landscape of Competing Endogenous RNA Networks in Sepsis-Induced Cardiovascular Diseases

“…The lncRNA-mediated ceRNA networks regulate cardiovascular toxicity in sepsis as shown in Tables 1 , 2 (Ref. [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]).…”

“…Both in vivo and in vitro experiments indicated that NEAT1 was an upstream regulator of NF- B and a ceRNA of miR-144-3p . The lncRNA MAP kinase-activated protein kinase 5 antisense gene protein 1 ( MAPKAPK5-AS1 ) was significantly upregulated in LPS-treated SD rats and H9C2 cells [ 39 ]. Knockdown of MAPKAPK5-AS1 inhibited inflammatory response by targeting miR-124-3p to downregulate the expression of E2F3.…”