Soheila Talesh Sasani

BACE1 promotes aggregation of β-amyloid in Alzheimer’s patients’ brains. MicroRNAs play roles in gene expression regulation. Furthermore, BACE1 is a target for microRNAs. There is a crosstalk between the peripheral and central immune systems in the etiology of Alzheimer’s disease. This study investigates the alterations in expression of BACE1, along with miR-15a-5p and miR-19b-3p genes, in peripheral blood mononuclear cells (PBMCs) of late-onset Alzheimer’s disease (LOAD) patients. The levels of BACE1 mRNA, miR-15a-5p, and miR-19b-3p were measured in PBMCs using a real-time quantitative PCR method. Cytoscape software was used to identify the putative target genes of these microRNAs. Significant increase in BACE1 levels (mean ± SD: 2.076 ± 0.5308), and decrease in both miR-15a-5p and miR-19b-3p expressions (0.3656 ± 0.1056 and 0.7296 ± 0.1933, respectively) were observed. Altered BACE1, miR-15a-5p, and miR-19b-3p expressions suggest novel indicators for early LOAD diagnosis. We illustrated target genes by which these microRNAs may regulate BACE1 expression.

Breast cancer (BC) is the main cause of cancer-related death in women worldwide. We evaluated the association between the key CCND1 gene variant; rs9344 (G>A); and BC risk in Iran. In this case-control study, blood samples were obtained from 58 patients and 66 healthy controls. Genotyping was conducted by tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR). Statistical analysis was performed by MedCalc software. Our results showed that the polymorphism rs9344 has an association with BC risk in the Iranian population. Based on the codominant and recessive models, carriers of the AA genotype are nearly 3.5 times more susceptible to BC than other individuals, and the AA genotype of CCND1 A870G may be a significant factor for breast cancer. Further studies are needed to clarify the roles of CCND1 polymorphism, rs9344, in breast cancer.

Background Breast cancer is one of the most decisive causes of cancer death in women worldwide. Cancer progression and tumor metastasis depend on angiogenesis. Vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) are critically required for tumor angiogenesis. Src is involved in many of the VEGF-mediated pathways. The VEGFRs activate Src via different mechanisms. Given that Src activates STAT3 (signal transducers and activators of transcription) repressing apoptosis and promoting the cell cycle, it may be an important object for cancer treatment. Methods and results A series of VEGF antagonistic peptides, referred to as VGB 1,3 and 4, were designed to bind and block both VEGFR1 and VEGFR2 inhibiting the proliferation of different tumoral cells. We investigated c-Src and STAT3 gene expression changes in murine 4T1 tumors treated by the VGBs. The treated group received 1 and 10 mg kg⁻¹ of the peptides, while the control mice received PBS, intraperitoneally for two weeks. Both of the groups underwent a resection of breast tissue 14 days after treatment. The results of qRT-PCR showed that the expression levels of c-Src and STAT3 genes were significantly decreased, in a dose-dependent manner, after treatment with the different types of VEGF antagonist peptides, compared to the control groups (P < 0.05). The groups treated with 1 mg kg⁻¹ of all three types of VGB showed decreased expression of c-Src and STAT3 less than the groups receiving 10 mg kg⁻¹ of the anti-angiogenic peptides. Conclusions In conclusion, peptides VGB1, 3, and 4, could be effective therapeutic molecules in breast cancer by inhibiting angiogenesis and progression of the disease.

Background: Breast cancer (BC) is one of the main causes of cancer-related death in women worldwide. It is necessary to find methods for prognosis and early detection of BC. MicroRNAs inhibit the expression of special target genes at the post-transcriptional stage and have a fundamental role in various cancers. They function as oncogenes or tumor suppressors. MiR-125a- 5p acts as a tumor suppressor in some cancers through a signal transducer and activator of transcription 3 (STAT3) suppression. STAT3 is activated in response to cytokines and growth factors, affecting the transcription of target genes. Objective: We examined the association between miR-125a-5p and STAT3 expression levels in breast cancer patients for the first time through a case-control study on an Iranian population. Methods: Total RNAs were extracted from breast cancer and healthy tissues using TRIzol Reagent. Complementary DNA synthesis was performed, and Real-time PCR was done using miR-125a and STAT3-specific primers. GAPDH and U48 genes were used as internal controls. Statistical analysis of the results was conducted by SPSS v.19.0 software. Results: We obtained a significant association between miR-125a-5p down-regulation and breast cancer disease (0.4333 in patients vs. 1.656 in controls, p-value = 0.009). STAT3 expression was significantly up-regulated in BC samples relative to healthy subjects (1.324 vs. 0.6557, respectively) and p-value <0.0001. Conclusion: We investigated that decreased miR-125a-5p expression levels were significantly associated with increased STAT3 expression in BC tissues. Therefore, the expression changes of miR- 125a-5p can be an important potential biomarker for early diagnosis of breast cancer. Also, the miRNA molecule may have serious therapeutic potential.

Considering the role of miR-146a in the control of inflammation, we assessed the importance of two miR-146a polymorphisms (rs2910164 and rs57095329) in the development and severity of ulcerative colitis (UC) in Iran. Genomic DNA of 150 cases with UC and 200 healthy individuals were genotyped using the PCR-RFLP technique. Statistical analyses were performed using Med Calc software. The miR-146a rs2910164 C allele was significantly associated with increased risk of UC. Individuals carrying the CC (rs2910164) were more than fourfold higher risk of UC relative to wild type homozygotes. The combined GC + CC genotypes were also associated with increased UC risk. We also found that the rs2910164 CC genotype was associated with a severe form of the disease However, the distribution of variant allele and genotypes of rs57095329 did not differ between the cases and controls. In conclusion, miR-146a rs2910164 polymorphism may play a role in UC. To confirm our findings, additional well-designed studies in diverse ethnic populations are required.

Background: Hepatocyte Growth Factor (HGF) and its receptor, Mesothelial-Epithelial Transition (cMet) factor signaling, play an essential role in controlling synaptogenesis. Objectives: Because of the vital role of HGF and Met signaling in synaptogenesis and spatial learning function of the brain’s hippocampal region, we aimed to study the HGF and soluble ...

Background Breast and gastric cancers are the most important diseases that lead to cancer death and social healthcare challenge. Overexpression of PBX1, a proto-oncogene, is correlated with the progression and metastasis of various cancers. For the first time, in this study the researchers evaluated the relationship between rs6426881, affecting miR-522-3p binding to the PBX1, with breast and gastric cancers. Methods and results The Microarray analysis was performed for finding the relative expression level of PBX1 and hsa-miR-522-3p, based on high throughput experiments. The GSE54397, GSE112369, GSE10810, GSE241585.ER, GSE24185.PR, GSE68373, and GSE38167 datasets were analyzed. A case-control study was carried out in 123 Iranian suffering from breast cancer and 132 participants as control samples as well as 130 people suffering from gastric cancer and 54 people as control group members. SNP rs6426881 in the 3′-UTR of PBX1 was genotyped by the High-Resolution Melting (HRM) method. Association analysis revealed that rs6426881 is correlated with Estrogen and Progesterone receptors, grade, and stage of breast cancer. Furthermore, a significant relationship was observed between the genotypes and blood groups in gastric cancer, while the distribution of alleles was significantly related to smoking, status of the primary tumor, and metastasis (Chi-Square P < 0.05). Finally, Bioinformatics analyses suggested that rs6426881 contains binding sites for miR-522-3p in the 3′-UTR of PBX1 transcript. The finding suggested that TT genotype is associated with poor prognosis in breast and gastric cancer. Conclusions The rs6426881 T allele at PBX1 3′-UT is significantly related to breast and gastric cancers by altering the regulatory affinity of miR-522-3p to PBX1 3′-UTR and may be suggested as a novel prognostic biomarker for the diseases.

Breast cancer is the fourth common cancer worldwide and occurs when breast cells begin to uncontrolled division and tumor formation. Angiogenesis is one of the essential factors in cell growth and maintenance of homeostasis in the natural and pathological conditions, while VEGFs are the most critical factors in angiogenesis. MiR-210 ...