ABSTRACT
DNA methylation is also involved in the development and progression of cardiac diseases. Although studies have shown that DNA methylation and RNA m6A methylation play an important role in the development of myocardial hypertrophy, whether DNA methylation and RNA m6A methylation have a coordinated role in the development of myocardial hypertrophy and influence each other is still unknown. Here, we found that DNMT1 expression was downregulated in TAC mice and Ang II-treated NRCMs. Moreover, DNMT1 overexpression inhibited Ang II-induced apoptosis of NRCMs. Furthermore, we found that the expression of METTL3 was up-regulated after inhibiting the expression of DNMT1 by a DNMT1 inhibitor or small interfering RNA. In addition, ectopic expression DNMT1 inhibited METTL3 expression in NRCMs. Furthermore, METTL3 expression was elevated in NRCMs treated with Ang II, and suppression of METTL3 inhibited cell apoptosis induced by Ang II in NRCMs.In addition, this study revealed that the DNMT1/METTL3 pathway affected Ang II-induced apoptosis in NRCMs. Finally, this study found that DNMT1, but not METTL3, might directly regulated the ANP and BNP expression. Collectively, our findings revealed the role of the DNMT1/METTL3 pathway in cardiac hypertrophy and provided a novel molecular mechanism describing the physiological and pathological processes.
ABSTRACT
BACKGROUND: Serum gamma-glutamyltransferase (GGT) has been reported to be correlated with survival in a variety of malignancies. However, its effect on patients with bladder cancer (BC) treated by radical cystectomy has never been evaluated. PATIENTS AND METHODS: We retrospectively evaluated 263 patients who underwent radical surgery in our center. Baseline features, hematologic variables, and follow-up data were obtained. The endpoints included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). The relationship between GGT and survival were evaluated. RESULTS: The median follow-up period for all patients was 34.7 (22.9-45.9) months. At the last follow-up, 67 patients died, 51 patients died of cancer, 92 patients experienced disease recurrence. Patients with an elevated serum GGT had a higher rate of pT3-T4 tumors. Patients with a higher preoperative serum GGT had a lower rate of OS, CSS and DFS (P < 0.001 for all). Multivariate analysis identified that preoperative serum GGT was independent predictor of OS (HR: 3.027, 95% CI: 1.716-5.338; P < 0.001), CSS (HR: 2.115, 95% CI: 1.093-4.090; P = 0.026), DFS (HR: 2.584, 95% CI: 1.569-4.255; P < 0.001). Age, diabetes history, pathologic T stage, and lymph node status also were independent predictors of prognosis for BC patients. CONCLUSIONS: Our results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.
ABSTRACT
BACKGROUND: To investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa). PATIENTS AND METHODS: A cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). RESULTS: After a median 34.2 (22.9-45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524-6.358; Pâ¯=â¯0.002), CSS (HR: 4.564, 95% CI: 2.008-10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125-3.739; Pâ¯=â¯0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis. CONCLUSIONS: Preoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.
