Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes.

The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies

Serum ox-LDL Level is Reduced with the Extent of Stenosis in Coronary Arteries

Oxidized LDL (ox-LDL) lipoproteins are proposed as important modified particles triggering pro-inflammatory events through receptor-mediated pathways. We evaluated the circulating ox-LDL level on the concept that the chronic immune events may affect ox-LDL clearance as the vessel stenosis develops in coronary arteries. One hundred sixty five subjects underwent coronary angiography and then, subdivided into four subgroups controls (n=85); SVD, 2VD and 3VD (n=80). The serum ox-LDL level and other biochemical parameters were measured using ELISA method and routine laboratory techniques, respectively. The serum ox-LDL level in the control group (4.81±1.41 mU/mg) was significantly higher than patients (4.28±1.73 mU/mg, P<0.05). The ox-LDL/LDL ratio was conversely reduced with the extent of stenosis as compared with the controls (P<0.05). Furthermore, no difference was observed in the ox-LDL/LDL ratio between the 2VD and 3VD patients. We suggested the atherosclerosis process increases the total clearing capacities of the circulating ox-LDL particles

Association of Lin-28A rs3811464 Variant with Susceptibility to Type 2 Diabetes

Introduction: It has been suggested that Lin-28A and the let-7 microRNA family (Lin-28/let-7 axis) play a critical role in the control of glucose metabolism, insulin sensitivity and resistance to diabetes. Aim: This case-control study aimed at evaluating the association between Lin-28 rs3811464 polymorphism and the susceptibility to Type 2 Diabetes (T2D) in a sample of Iranian population. Materials and Methods: This study involved 172 T2D patients and 160 non-diabetic age and gender-matched controls. Lin 28A rs3811464 genotypes were determined by Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Results: The results showed that the frequency of the AA genotype was significantly higher in control subjects than in diabetic patients (13.12% vs. 4.65%). In addition, binary logistic regression analysis revealed that rs3811464-AA genotype was significantly associated to T2D after adjustment for BMI, age and lipid profiles. Indeed, subjects with AA genotype were less likely to develop T2D than GG and AG subjects (OR of 0.26, 95% CI 0.10-0.66, p=0.005). Conclusion: The findings of our study suggest that the Lin 28A rs3811464 is associated with type 2 diabetes susceptibility and subjects with AA genotypes were less likely to develop T2D diabetes

Multi-Drug Resistance against Second-Line Medication and MicroRNA Plasma Level in Metastatic Breast Cancer Patients

Background: Circulating microRNAs (miRNAs) can help to predict the chemotherapy response in breast cancer with promising results. The aim of the present study was to investigate the relationships between the miR-199a, miR-663a, and miR-663b expression and chemotherapy response in metastatic breast cancer patients.Methods: This study is a case-control study performed at Yasuj University of Medical Sciences (2018-2021). The expression levels of miR-663a, miR-663b, and miR-199a in the serum of 25 patients with metastatic breast cancer versus 15 healthy individuals were determined by the real-time polymerase chain reaction method. The response to treatment was followed up in a 24-month period. All patients were treated with second-line medications. Two or more combinations of these drugs were used: gemcitabine, Navelbine®, Diphereline®, Xeloda®, letrozole, Aromasin®, and Zolena®. Statistical analyses were performed in SPSS 21.0 and GraphPad Prism 6 software. The expression levels were presented as mean±SD and analyzed by Student’s t test.Results: The results and clinicopathological features of patients were analyzed by t test. The statistical analysis showed that miR-663a expression was related to human epidermal growth factor receptor 2 (HER2) status and was significantly lower in the HER2+ than HER2- group (P=0.027). Moreover, the expression of miR-199a and miR-663b was significantly correlated with the response to treatment, in which the expression of miR-199a was higher in the poor-response group (P=0.049), while the higher expression of miR-663b was seen in the good-response group (P=0.009).Conclusion: These findings state that the high plasma level of miR-199a and the low plasma level of miR-663b may be related to chemoresistance in patients with metastatic breast cancer