ETS2 promotes cardiomyocyte apoptosis and autophagy in heart failure by regulating lncRNA TUG1/miR‐129‐5p/ATG7 axis

Abstract

Heart failure (HF) is a chronic disease in which the heart is unable to provide enough blood and oxygen to the peripheral tissues. Cardiomyocyte apoptosis and autophagy have been linked to HF progression. However, the underlying mechanism of HF is unknown. In this study, H 2 O 2 -treated AC16 cells were used as a cell model of HF. The mRNA and protein levels of related genes were examined using RT-qPCR and western blot. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry, respectively. The interactions between ETS2, TUG1, miR-129-5p, and ATG7 were validated by luciferase activity, ChIP, and RNA-Binding protein Immunoprecipitation assays. According to our findings, H 2 O 2 stimulation increased the expression of ETS2, TUG1, and ATG7 while decreasing the expression of miR-129-5p in AC16 cells. Furthermore, H 2 O 2 stimulation induced cardiomyocyte apoptosis and autophagy, which were reversed by ETS2 depletion, TUG1 silencing, or miR-129-5p upregulation. Mechanistically, ETS2 promoted TUG1 expression by binding to the TUG1 promoter, and TUG1 sponged miR-129-5p to increase ATG7 expression. Furthermore, TUG1 overexpression reversed ETS2 knockdown-mediated inhibition of cardiomyocyte apoptosis and autophagy and miR-129-5p inhibition abolished TUG1 depletion-mediated suppression of cardiomyocyte apoptosis and autophagy in H 2 O 2 -induced AC16 cells.As presumed, ATG7 overexpression reversed miR-129-5p mimics-mediated repression of cardiomyocyte apoptosis and autophagy in H 2 O 2 -induced AC16 cells.Finally, ETS2 silencing reduced cardiomyocyte apoptosis and autophagy to slow HF progression by targeting the ETS2/TUG1/miR-129-5p/ATG7 axis, which may provide new therapeutic targets for HF treatment.

ETV7 promotes colorectal cancer progression through upregulation of IFIT3

“…Yan et al reported that overexpression of ELK1 increased pancreatic cancer cells proliferation, invasion, and survival (Yan et al 2021 ). Tan et al revealed that ETS2 silencing reduced cardiomyocyte apoptosis and autophagy to slow Heart failure (HF) progression(Tan et al 2023 ).…”

Efeito Protetor do RNA Não Codificante Longo OXCT1-AS1 na Apoptose de Células Miocárdicas Humanas Induzida pela Doxorrubicina pelo Padrão Competitivo de RNA Endógeno

“…A insuficiência cardíaca (IC) é uma síndrome clínica complexa caracterizada por disfunção sistólica e diastólica. 1 É o resultado final da transformação de diversas doenças cardiovasculares e está associada a altas taxas de morbidade e mortalidade. 2 A apoptose de cardiomiócitos causa a perda de cardiomiócitos e leva à baixa contratilidade miocárdica.…”

“…Heart failure (HF) is a complex clinical syndrome characterized by systolic and diastolic dysfunction. 1 It is the ultimate transformation result of various cardiovascular diseases and is associated with high morbidity and mortality rates. 2 Cardiomyocyte apoptosis causes the loss of cardiomyocytes and leads to poor myocardial contractility.…”

Cardiomyocyte Autophagy: A Novel Therapeutic Target by LncRNA PART1

“… 7) A transcription factor ETS2 modulated the lncRNA TUG1/miR-1205p/ATG7 axis to promote heart failure progression by inducing cell apoptosis and autophagy. 8) …”