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Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial-mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a Cancer Stem Cell (CSC) model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis. The miRNAs are related to epigenetic event and additionally affect epigenetic pathways. Recent evidence demonstrates that epigenetic mechanisms such as DNA methylation may control miRNA expression. Because each miRNA may regulate several target genes, dysregulation of miRNA caused by aberrant DNA methylation patterns of the locus may influence important downstream pathways. Furthermore, some miRNAs is believed to regulate important DNA methylator factors. Any disruption or modification of this intricate network can contribute to the disease process; thus, it is essential to understand these changes. Advancements in new sequencing technologies to detect DNA methylation patterns has provided the opportunity to determine differentially methylated regions (DMRs) of the miRNA locus and their effect on expression profiles to improve BC diagnosis and treatment. The current review examines the interplay of DNA methylation mechanisms and miRNA function in invasive tumorigenesis, specifically EMT and CSC of BC, to highlight its potential for advancements on BC etiology, diagnosis, and therapy.

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BackgroundThe health benefits of pomegranate juice have been reported in several studies. However, limited clinical trials have examined the effects of concentrated pomegranate juice (CPJ) on inflammatory factors.ObjectivesThis study aimed to investigate the effects of CPJ on metabolic risk factors, including inflammatory biomarkers, in patients with type 2 diabetes mellitus.Patients and MethodsIn a quasi-experiment trial, 40 type 2 diabetic patients were asked to consume 50 g of CPJ daily for 4 weeks. Anthropometric indices, dietary intake, blood pressure measurements, and fasting blood samples were conducted at baseline and 4 weeks after the intervention.ResultsThe intake of CPJ produced a significant increase in both total and high-density lipoprotein cholesterol (HDL-C) (4.7% and 3.9%, respectively) from baseline (P < 0.05). However, changes that were observed in serum triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose, and blood pressure were not statistically significant. Administration of CPJ caused significant reduction in serum interleukin-6 (IL-6) (P < 0.05), but tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) remained unchanged during the study. The mean value of serum total antioxidant capacity (TAC) was substantially increased (~ 75%) from 381.88 ± 114.4 at baseline to 1501 ± 817 after 4 weeks of CPJ consumption.ConclusionsConsumption of CPJ (50 g/day) appears to have favorable effects on some markers of subclinical inflammation, and to increase plasma concentrations of antioxidants in patients with type 2 diabetes.

BackgroundSquamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (APC) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of APC promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and APC promoter methylation.MethodsFor evaluating the status of APC promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated APC promoter was compared with that of unmethylated patients.ResultsAssessment of APC promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of APC. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of APC. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated APC promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.ConclusionObserving similar level of APC promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated APC promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.

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Tropomyosins (TMs) are a family of cytoskeletal proteins that bind to and stabilize actin microfilaments. Non-muscle cells express multiple isoforms of TMs including three high molecular weight (HMW) isoforms: TM1, TM2, and TM3. While reports have indicated downregulation of TMs in transformed cells and several human cancers, nevertheless, little is known about the underlying mechanism of TMs suppression. In present study the expression of HMW TMs was investigated in squamous cell carcinoma of esophagus (SCCE), relative to primary cell cultures of normal esophagus by western blotting and real-time RT-PCR. Our results showed that TM1, TM2, and TM3 were significantly downregulated in cell line of SCCE. Moreover, mRNA level of TPM1 and TPM2 were markedly decreased by 93% and 96%, in tumor cell line relative to esophagus normal epithelial cells. Therefore, downregulation of TMs could play an important role in tumorigenesis of esophageal cancer. To asses the mechanism of TM downregulation in esophageal cancer, the role of Ras dependent signaling and promoter hypermethylation were investigated. We found that inhibition of two Ras effectory downstream pathways; MEK/ERK and PI3K/Akt leads to significant increased expression of TM1 protein and both TPM1 and TPM2 mRNAs. In addition, methyltransferase inhibition significantly upregulated TM1, suggesting the prominent contribution of promoter hypermethylation in TM1 downregulation in esophageal cancer. These data indicate that downregulation of HMW TMs occurs basically in SCCE and the activation of MEK/ERK and PI3K/Akt pathways as well as the epigenetic mechanism of promoter hypermethylation play important role in TM1 suppression in SCCE.