A number of studies have attempted to elucidate the association between mircoRNAs (miRNAs/miRs) and cancer-associated processes. The aim of the present study was to determine how miR-499a-5p intervenes in human osteosarcoma cell proliferation and differentiation. The cancerous tissues and adjacent non-cancerous tissues of 62 patients with osteosarcoma (OS) were collected. miRNA microarray analysis revealed that 29 miRNAs were upregulated while 26 were downregulated, among which miR-499a-5p expression was the most decreased. Western blot analysis and reverse transcription-quantitative polymerase chain reaction demonstrated that the mRNA and protein expression of miR-499a-5p was lower, while that of protein phosphatase 1D (PPM1D) was higher in OS tissues compared with expression levels in normal tissues. Furthermore, miR-499a-5p expression was markedly decreased in the metastatic tumors and in those at stage III+IV compared with the non-metastatic tumors and those at stage I, respectively. In addition, following transfection of the human OS MG-63 cell line with an miR-499a-5p mimic, the expression of miR-499a-5p was elevated while the protein and mRNA expression of PPM1D was decreased. When combining these findings with the information obtained from the Targetscan predictive software, it was confirmed that PPM1D was targeted by miR-499a-5p. In MG-63 cells transfected with an miR-499a-5p mimic, PPM1D-associated downstream proteins phosphorylated protein kinase B (p-Akt) and phosphorylated glycogen synthase kinase 3β (p-GSK-3β) were significantly downregulated compared with the negative control (NC) group, while the expression of p-Akt and p-GSK-3β were significantly elevated in the tumor tissues compared with the adjacent non-tumor tissues. Simultaneously, the growth and proliferation activity of MG-63 cells were notably reduced when transfected with the miR-499a-5p mimic, compared with the NC group. Therefore, it may be concluded that miR-499a-5p suppresses OS cell proliferation and differentiation by targeting PPM1D through modulation of Akt/GSK-3β signaling.

ObjectiveNumerous studies have suggested that microRNA-126 (miR-126) is involved in development of various cancer types as well as in malignant proliferation and invasion. However, its role in human prostate cancer (PCa) is still unclear. The aim of this study was to investigate miR-126 expression in PCa and its prognostic value for PCa patients undergoing radical prostatectomy.MethodsA series of 128 cases with PCa were evaluated for the expression levels of miR-126 by quantitative reverse-transcription PCR (qRT-PCR). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between miR-126 expression and prognosis of PCa patients.ResultsCompared with non-cancerous prostate tissues, the expression level of miR-126 was significantly decreased in PCa tissues (PCa vs. non-cancerous prostate: 1.05 ± 0.63 vs. 2.92 ± 0.98, P < 0.001). Additionally, the loss of miR-126 expression was dramatically associated with aggressive clinical pathological features, including advanced pathological stage (P = 0.001), positive lymph node metastasis (P = 0.006), high preoperative PSA (P = 0.003) and positive angiolymphatic invasion (P = 0.001). Moreover, Kaplan–Meier survival analysis showed that PCa patients with low miR-126 expression have shorter biochemical recurrence (BCR)-free survival than those with high miR-126 expression. Furthermore, multivariate analysis indicated that miR-126 expression was an independent prognostic factor for BCR-free survival after radical prostatectomy.ConclusionThese findings suggest for the first time that the loss of miR-126 expression may play a positive role in the malignant progression of PCa. More importantly, the downregulation of miR-126 may serve as an independent predictor of BCR-free survival in patients with PCa.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1740080792113255.

Background Right ventricular restrictive physiology (RVRP) is a common finding after repair of Tetralogy of Fallot (TOF). The characteristic feature of RVRP is the presence of a direct end-diastolic flow (EDFF) during atrial contraction in the main pulmonary artery. This end-diastolic forward flow is caused by increased right ventricular end-diastolic pressure due to right ventricular myocardial stiffness and decreased right ventricular compliance. Objective Our main objective is to found out the etiology of RVRP in pediatrics patients who underwent for complete repair of Tetralogy of Fallot (TOF). Methods A total of 50 TOF patients have registered for this study in our hospital from January 2017 to September 2018. The patients were divided in two groups, group A with restrictive physiology and group B without restrictive physiology. The patients selected for this study includes TOF patients, TOF patients with atrial septal defect (ASD), and TOF patients with patent ductus arteriosus (PDA). Ventricular hypertrophy and right heart enlargement were evaluated by electrocardiogram and echocardiography. The other parameters we used to compare between these two groups were sex, age, weight, cardio pulmonary bypass (CPB) time, aortic cross clamping time, transannular patch, SP0 2 , RV/LV pressure, ventricular hypertrophy, right heart (RH) enlargement, tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), TAPSE/PASP ratio, pulmonary annular diameter, intubation time, PICU stay and hematocrit (HCT). Results RVRP was identified in 28 patients (58%). Lower SP0 2 (mean: 84.3 ± 7.9%) with p -value 0.015, transannular patch repair ( n = 22, 78.5%) with p-value< 0.001, longer cardiopulmonary bypass (CPB) time (mean: 117.6 ± 23 min) with p-value< 0.001, longer aortic cross clamping time (mean: 91.4 ± 20.26 min) with p-value< 0.001, lower TAPSE, lower PASP,lower TAPSE/PASP ratio and presence of hypertrophy (p-value < 0.001) were identified as etiology for restrictive physiology. It was also found that 77% TOF patients with ASD have a higher risk of RVRP in our study. Conclusions In TOF patient’s etiology for right ventricular restrictive physiology are associated with lower SP0 2, transannular patch repair, longer CPB and longer aortic cross clamping time, hypertrophy, lower TAPSE, lower PASP and lower TAPSE/PASP ratio.