Dataset Information

LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1.

ABSTRACT: Myocardial injury is a frequently occurring complication of sepsis. This study aims to investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1)-mediated DNA methyltransferase 1/B-cell lymphoma-2 (DNMT1/Bcl-2) axis in sepsis-induced myocardial injury. Mice and HL-1 cells were treated with lipopolysaccharide (LPS) to establish animal and cellular models simulating sepsis and inflammation. LncRNA SNHG1 was screened out as a differentially expressed lncRNA in sepsis samples through microarray profiling, and the upregulated expression of lncRNA SNHG1 was confirmed in myocardial tissues of LPS-induced septic mice and HL-1 cells. Further experiments suggested that silencing of lncRNA SNHG1 reduced the inflammation and apoptotic rate of LPS-induced HL-1 cells. LncRNA SNHG1 inhibited Bcl-2 expression by recruiting DNMT1 to Bcl-2 promoter region to cause methylation. Inhibition of Bcl-2 promoter methylation reduced the inflammation and apoptotic rate of LPS-induced HL-1 cells. In vivo experiments substantiated that lncRNA SNHG1 silencing alleviated sepsis-induced myocardial injury in mice. Taken together, lncRNA SNHG1 promotes LPS-induced myocardial injury in septic mice by downregulating Bcl-2 through DNMT1-mediated Bcl-2 methylation.

SUBMITTER: Zhang R

PROVIDER: S-EPMC9258699 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1.

Zhang Rui R Niu Zequn Z Liu Jie J Dang Xiaoyan X Feng Hui H Sun Jiangli J Pan Longfei L Peng Zhuo Z

Journal of cellular and molecular medicine 20220609 13

Myocardial injury is a frequently occurring complication of sepsis. This study aims to investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1)-mediated DNA methyltransferase 1/B-cell lymphoma-2 (DNMT1/Bcl-2) axis in sepsis-induced myocardial injury. Mice and HL-1 cells were treated with lipopolysaccharide (LPS) to establish animal and cellular models simulating sepsis and inflammation. LncRNA SNHG1 was screened out as a differentially expressed ...[more]

PMID: 35678255

Similar Datasets

Project description:The increasing rates of morbidity and mortality caused by ischemic heart disease pose a serious threat to human health. Long non‑coding (lnc)RNA small nucleolar RNA host gene 1 (SNHG1) has a protective effect on the myocardium. In the present study, the role of lncRNA SNHG1 in myocardial ischemia reperfusion injury (MIRI) and the underlying mechanisms were investigated. After hypoxia/reoxygenation (H/R) induction, the expression levels of lncRNA SNHG1 were detected using reverse transcription‑quantitative PCR. After lncRNA SNHG1 overexpression via cell transfection, cell viability was detected using an MTT assay, apoptotic rates were detected using TUNEL staining, apoptosis‑related protein expression levels were detected using western blotting and respective kits were used to measure the oxidative stress levels. The Encyclopedia of RNA Interactomes database predicted the presence of binding sites between lncRNA SNHG1 and microRNA (miR)‑450b‑5p, and between miR‑450b‑5p and insulin‑like growth factor 1 (IGF1). These interactions were then verified using luciferase reporter assays. Subsequently, the regulatory mechanism underlying the lncRNA SNHG1/miR‑450b‑5p/IGF1 axis in MIRI was investigated by overexpressing miR‑450b‑5p and knocking down IGF1 expression in H/R‑induced cells. Finally, the expression of PI3K/Akt signaling pathway‑related proteins was detected using western blotting. lncRNA SNHG1 expression was significantly downregulated in H/R‑induced AC16 cells. lncRNA SNHG1 overexpression significantly inhibited apoptosis and decreased oxidative stress levels in H/R‑induced AC16 cells, which was mediated via regulation of the miR‑450b‑5p/IGF1 axis and activation of the PI3K/Akt signaling pathway. Therefore, the present study suggested that activation of the PI3K/Akt signaling pathway via the lncRNA SNHG1/miR‑450b‑5p/IGF1 axis inhibited the apoptosis and oxidative stress levels of H/R‑induced AC16 cells.

Project description:Rationale: Most current cardiac regeneration approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to determine whether the lncRNA small nucleolar RNA host gene 1 Snhg1 (Snhg1) could form a positive feedback loop with c-Myc to induce cardiac regeneration. Methods: Quantitative PCR and in situ hybridization experiments were performed to determine the Snhg1 expression patterns in fetal and myocardial infarction (MI) hearts. Gain- and Loss-of-function assays were conducted to explore the effect of Snhg1 on cardiomyocyte (CM) proliferation and cardiac repair following MI. We further constructed CM-specific Snhg1 knockout mice to confirm the proliferative effect exerted by Snhg1 using CRISPR/Cas9 technology. RNA sequencing and RNA pulldown were performed to explore how Snhg1 mediated cardiac regeneration. Chromatin immunoprecipitation and luciferase reporter assays were used to demonstrate the positive feedback loop between Snhg1 and c-Myc. Results: Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Overexpression of Snhg1 promoted CM proliferation, angiogenesis, and inhibited CM apoptosis after myocardial infarction, which further improved post-MI cardiac function. Antagonism of Snhg1 in early postnatal mice inhibited CM proliferation and impaired cardiac repair after MI. Mechanistically, Snhg1 directly bound to phosphatase and tensin homolog (PTEN) and induced PTEN degradation, activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote CM proliferation. The c-Myc protein, one of downstream targets of PI3K/AKT signaling, functioned as a transcription factor by binding to the promoter regions of Snhg1. Perturbation of the positive feedback between Snhg1 and c-Myc by mutation of the binding sequence significantly affected Snhg1-induced CM proliferation. Conclusions: Snhg1 effectively elicited CM proliferation and improved cardiac function post-MI by forming a positive feedback loop with c-Myc to sustain PI3K/Akt signaling activation, and thus may be a promising cardiac regeneration strategy in treating heart failure post-MI.

Dataset Information

LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1.

Publications

LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets