RESUMO
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, H2 O2 -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, H2 O2 stimulation increased the expression of ETS2, TUG1, and ATG7 while decreasing the expression of miR-129-5p in AC16 cells. Furthermore, H2 O2 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 H2 O2 -induced AC16 cells. As presumed, ATG7 overexpression reversed miR-129-5p mimics-mediated repression of cardiomyocyte apoptosis and autophagy in H2 O2 -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.
Assuntos
Insuficiência Cardíaca , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Miócitos Cardíacos/metabolismo , Proliferação de Células/genética , Apoptose/genética , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Autofagia/genética , Proteína Proto-Oncogênica c-ets-2/genética , Proteína Proto-Oncogênica c-ets-2/metabolismo , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismoRESUMO
OBJECTIVES: To investigate the clinical significance of prognostic nutritional index (PNI) in predicting the efficacy in patients with B-cell lymphoma. METHODS: The clinical data from 111 patients with B-cell lymphoma (B-cell lymphoma group), who were newly diagnosed in the Third Xiangya Hospital of Central South University from February 2013 to September 2018, were retrospectively analyzed. A total of 93 volunteers selected from the Health Management Center in the Third Xiangya Hospital were set as control, The PNI was compared between the 2 groups. The PNI cut-off value was determined by receiver operating characteristic (ROC) curve analysis. According to the PNI values of patients before chemotherapy, the patients were also divided into a high PNI group (≥43.5) and a low PNI group (<43.5). The correlation of baseline characteristics was evaluated. The correlation between changes in PNI levels and efficacy were evaluated before and after chemotherapy. RESULTS: The PNI value in the B-cell lymphoma group was significantly lower than that in the healthy control group (P<0.05). Lactate dehydrogenase (LDH), presence or absence of B symptoms, international prognostic index (IPI), Eastern Cooperative Oncology Group (ECOG) performance status, source of germinal center, and the efficacy between the high PNI group and the low PNI group were significantly different (all P<0.05). The mean PNI in the effective patients in the low PNI group was increased from 38.10 before chemotherapy to 42.66 after chemotherapy, with significant difference (t=-2.562, P<0.05). The PNI value in the ineffective patients in the high PNI group was decreased from 50.50 before chemotherapy to 41.45 after chemotherapy, with significant difference (t=3.044, P<0.05). CONCLUSIONS: The level of PNI in patients with B-cell lymphoma is significantly lower than that in healthy people, and it is related to the baseline characteristics of prognosis. The change of PNI level before and after chemotherapy can provide certain basis for efficacy evaluation.
