RESUMO
MiR-145 has been shown to suppress cell invasiveness and proliferation in endometriosis, whereas prostate cancer-associated transcript 1 (PCAT1) was reported to act as a sponge of miR-145 with one single-nucleotide polymorphism (SNP), rs710886, located in the chromosomal segment of PCAT1. Therefore, this study aimed to explore the association between rs710886 SNP and the risk of endometriosis, as well as the effect of this SNP on the activation of the signaling pathway downstream of PCAT1. Real-time polymerase chain reaction (PCR) was performed to observe the expression of miR-145 in transfected cells, while Matrigel invasion chamber assays and MTT assay were conducted to examine the invasiveness/proliferation among different cell groups. Moreover, bioinformatics tools, luciferase assays, real-time PCR, and Western blot analysis were used to measure the expression of these target genes in the presence of miR-145. Finally, a statistical analysis was conducted to compare the genotypes of rs710886 SNP between fertile healthy women and infertile women with endometriosis. PCAT1 small interfering RNA (siRNA) evidently increased the expression of miR-145 but reduced the invasiveness/proliferation of cells. P-PCAT1 exhibited an opposite effect as that of PCAT1 siRNA, indicating PCAT1 could promote the proliferation and invasiveness of endometriosis stem cells via inhibiting the expression of miR-145. Meanwhile, FASCIN1, SOX2, MSI2, SERPINE1, and JAM-A were identified as target genes of miR-145 via computational analysis and luciferase assays. Finally, a significant genetic effect was observed in both the dominant (AG+GG vs AA) and recessive models (GG vs AG+AA), indicating the presence of an association between the genotype of SNP rs710886 and the risk of endometriosis. SNP rs710886 A>G could lower the expression of PCAT1, thus leading to the overexpression of miR-145. Highly expressed miR-145 would inhibit the invasiveness and proliferation of endometriosis stem cells via targeting specific genes, thus decreasing the risk of endometriosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Endometriose/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Ciclo Celular , Movimento Celular , Proliferação de Células , Endometriose/genética , Endometriose/metabolismo , Feminino , Humanos , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Células Tumorais CultivadasRESUMO
Background: Definitions of declined left ventricular ejection fraction (LVEF) vary across studies and research results concerning the association of mortality with declined LVEF are inconsistent. Thus, this study aimed to assess the impact of early worsening LVEF on mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and to establish independent predictors of early worsening LVEF. Methods and Results: A total of 1,418 consecutive patients with HFpEF with LVEF remeasurement from the Cardiorenal Improvement registry were included in this study. Worsening LVEF was defined as an absolute decline ≥ 5% from baseline LVEF within 3 to 12 months after discharge. The Cox and logistic regression analyses were performed to assess prognostic effects and predictors for worsening LVEF, respectively. Among 1,418 patients with HFpEF, 457 (32.2%) patients exhibited worsening LVEF. During a median follow-up of 3.2 years (interquartile range: 2.3-4.0 years), 92 (6.5%) patients died. Patients with HFpEF with worsening LVEF had higher mortality relative to those with nonworsening LVEF [9.2 vs. 5.2%; adjusted hazard ratio (aHR): 2.18, 95% CI: 1.35-3.52]. In the multivariate binary logistic regression analysis, baseline left ventricular end-diastolic dimension (LVEDD), LVEF, high-density lipoprotein cholesterol (HDL-C), atrial fibrillation (AF), and diabetes mellitus (DM) emerged as predictive factors of worsening LVEF. Conclusion: This study demonstrated that about one out of three patients with HFpEF experiences worsening LVEF during follow-up, which is associated with 2.2-fold increased mortality. Increased LVEDD and LVEF, low HDL-C levels, AF, and DM were predictors of worsening LVEF. Further studies are needed to prospectively assess the efficacy of early active management on prognosis in patients with HF with worsening LVEF. Registration: ClinicalTrials.gov, identifier NCT04407936.