Interaction of lncRNAs with mTOR in colorectal cancer: a systematic review.

Colorectal cancer (CRC) is the third most widespread cancer and the fourth leading lethal disease among different societies. It is thought that CRC accounts for about 10% of all newly diagnosed cancer cases with high-rate mortality. lncRNAs, belonging to non-coding RNAs, are involved in varied cell bioactivities. Emerging data have confirmed a significant alteration in lncRNA transcription under anaplastic conditions. This systematic review aimed to assess the possible influence of abnormal mTOR-associated lncRNAs in the tumorigenesis of colorectal tissue. In this study, the PRISMA guideline was utilized based on the systematic investigation of published articles from seven databases. Of the 200 entries, 24 articles met inclusion criteria and were used for subsequent analyses. Of note, 23 lncRNAs were prioritized in association with the mTOR signaling pathway with up-regulation (79.16%) and down-regulation (20.84%) trends. Based on the obtained data, mTOR can be stimulated or inhibited during CRC by the alteration of several lncRNAs. Determining the dynamic activity of mTOR and relevant signaling pathways via lncRNAs can help us progress novel molecular therapeutics and medications.

MicroRNA-143 act as a tumor suppressor microRNA in human lung cancer cells by inhibiting cell proliferation, invasion, and migration.

BACKGROUND/AIM: MicroRNAs play crucial roles in controlling cellular biological processes. miR-143 expression is usually downregulated in different cancers. In this study, we focused on exploring the role of miR143 in NSCLC development. METHODS: Bioinformatics analyses were used to detect the expression level of miR-143 in lung tumors. The cells were transfected by pCMV-miR-143 vectors. The efficacy of transfection was verified by Flow cytometry. The influence of miR-143 replacement on NSCLC cells migration, proliferation, and apoptosis was detected using wound-healing assay, MTT assay, and DAPI staining, respectively. RESULTS: MTT assay revealed that overexpression of miR143 inhibited cell growth and proliferation. Scratch assay results demonstrated that restoration of miR143 suppressed cell migration. The qRT-PCR assay was further used to detect the assumed relationship between miR143 and apoptotic and metastatic-related genes. CONCLUSION: The findings showed that miR-143 could reduce cell proliferation, invasion, and migration by reducing CXCR4, Vimentin, MMP-1, Snail-1, C-myc expression level, and increasing E-cadherin expression levels in lung cancer cells and might be a potential target in NSCLC's targeted therapy.

Genetic basis of acephalic spermatozoa syndrome, and intracytoplasmic sperm injection outcomes in infertile men: a systematic scoping review.

PURPOSE: Acephalic spermatozoa syndrome (ASS) is known as a severe type of teratozoospermia, defined as semen composed of mostly headless spermatozoa that affect male fertility. In this regard, this systematic review aimed to discuss gene variants associated with acephalic spermatozoa phenotype as well as the clinical outcomes of intracytoplasmic sperm injection (ICSI) treatment for the acephalic spermatozoa-associated male infertility. METHODS: A systematic search was performed on PubMed, Embase, Scopus, and Ovid databases until May 17, 2020. This systematic scoping review was reported in terms of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement. RESULTS: Twenty articles were included in this systematic review. Whole-exome and Sanger sequencing have helped in the identification of variants in SUN5, PMFBP1, BRDT, TSGA10, DNAH6, HOOK1, and CEP112 genes as possible causes of this phenotype in humans. The results of the ICSI are conflicting due to both positive and negative reports of ICSI outcomes. CONCLUSION: ASS has a genetic origin, and several genetic alterations related to the pathogenesis of this anomaly have been recently identified. Notably, only SUN5 and PMFBP1 mutations are well-known to be implicated in ASS. Accordingly, more functional studies are needed to confirm the pathogenicity of other variants. ICSI could provide a promising treatment for acephalic spermatozoa-associated male infertility. Besides the importance of sperm head-tail junction integrity, some other factors, whether within the sperm cell or female factors, may be involved in the ICSI outcome.

Mediterranean fever (MEFV) gene profile and a novel missense mutation (P313H) in Iranian Azari-Turkish patients.

BACKGROUND: Familial Mediterranean fever (FMF) is common in Azari-Turkish people, one of the biggest ethnic groups in Iran. In this study, we sought to investigate the mutation spectrum of the MEFV gene and any genotype-phenotype correlations. METHODS AND MATERIALS: 400 unrelated Azari-Turkish FMF patients were analyzed in this study. Mutations in exons 2, 3, 5, and 10 of the MEFV gene were investigated using direct Sanger sequencing, and their correlations with the clinical features of the patients were analyzed. RESULTS: At least one mutation was detected in 248 (62%) patients. The most common mutations were M694V (26.25%) and E148Q (24.75%), respectively. Abdominal pain (65.2%) and fever 204 (51%) were the most frequent clinical problems in all subjects. The analysis recognized a novel missense mutation in the coding region of the MEFV gene, named P313H, which is the first report of a new mutation in exon 2 of the MEFV gene in an Azari-Turkish family. CONCLUSION: Genotype-phenotype correlations obtained from this study would be helpful in the diagnosis and management of FMF patients in clinical situations. This novel missense mutation may provide useful evidence for further studies of FMF pathogenesis.

Evaluation of DNA methylation status of toll-like receptors 2 and 4 promoters in Behcet's disease.

BACKGROUND: Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD. METHODS: In the present study, Iranian Azeri BD patients (n = 47) with an active (n = 22) and inactive (n = 25) period, and healthy controls (n = 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted. RESULTS: The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups. CONCLUSIONS: Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression.

Interleukin-17 mRNA expression and serum levels in Behçet's disease.

Behçet's disease (BD) was considered a T-helper 1 (Th1)-mediated autoimmune disease, but with the introduction of Th17 cells, their role in the pathogenesis of BD was also addressed. Despite studies on IL-17 in BD, the prognostic value of this cytokine in BD is unclear. The aim of this study is to determine the IL-17 mRNA expression rate and serum levels in patients with BD and its correlation with clinical manifestations and activity of BD. Forty-six BD patients in the active phase of the disease and 70 healthy controls were recruited in this study. BD activity was measured by Behçet's disease current activity form (BDCAF), Iranian Behçet's disease dynamic activity measure (IBDDAM) and total inflammatory activity index (TIAI). The IL-17 mRNA expression and serum levels were significantly higher in the BD patients compared with the healthy controls. These parameters in the BD patients aged <25 at disease onset, positive pathergy test, and positive HLA-B5 and HA-B51 were significantly higher than the healthy controls (P < 0.05). The IL-17 serum level in the patients with active uveitis was lower than the patients with in-active uveitis. There was no association between other clinical manifestations of BD and these parameters. No significant correlation was found between BDCAF and IBDDAM with IL-17 mRNA expression and serum levels. However, TIAI had a significant and negative correlation with the serum levels of IL-17.

Promoter methylation of Bax and Bcl2 genes and their expression in patients with Behcet's disease.

BCL2 and BAX genes are a group of signalling inducer and inhibitor genes playing a key role in the process of cellular physiological death (apoptosis). These genes, through the JAK/STAT signalling pathway, affect different cytokines on cell function and subsequently lead to the pathophysiology of diseases, especially autoimmune diseases. In addition, altering the methylation of genes can affect their expression. Since the aetiology and pathology of Behcet's disease is not fully understood, the aim of this study was to determine the methylation pattern of BCL2 and BAX genes in patients with Behcet's disease and compare it with those of control group. This was a case-control study on 51 patients with Behcet and 61 control subjects. Blood samples were received from all subjects. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method and the methylation of the sites was investigated using quantitative methylation specific PCR (qMS-PCR) technique after extraction of DNA by salting out method and its examination with Nano drop. The results of methylation and expression of Bax gene suggest that the methylation level in the patient group significantly increased compared to the healthy individuals (p-value < .05). Furthermore, the results related to Bax gene expression revealed that the mean of gene expression in the patient group has decreased compared to the healthy group, and this decrease was statistically significant (p-value < .05). The rate of expression and methylation of Bcl2 did not indicate any change in the two patient and healthy groups. Given the results of this study, it can be guessed that perhaps DNA methylation is involved in certain conditions of the disease and it may result in regulation of the expression of the involved genes such as Bax gene, in the pathogenesis of the disease.

MicroRNAs association with azoospermia, oligospermia, asthenozoospermia, and teratozoospermia: a systematic review.

Infertility is a major health problem across the world. One of the main reasons for male infertility are defects in sperm. Semen analysis is the most common test utilized to evaluate male fertility and since it suffers from multiple drawbacks, reproduction scientists have tried to find new molecular markers for detecting sperm defects. MicroRNAs (miRNAs) are small molecules in cells which take part in regulating gene expression. Various studies have confirmed miRNAs to have a role in defining multiple sperm characteristics, including sperm count, motility, and morphology. In this paper, we have systematically reviewed the role of miRNAs in infertile men with sperm defects including azoospermia, oligospermia, asthenozoospermia, and teratozoospermia. Also, we have assembled various bioinformatics tools to come up with a pipeline for predicting novel miRNAs which could possibly participate in sperm count, motility, and morphology. Also, related KEGG and GO terms for predicted miRNAs have been included in order to highlight their role in sperm function. Our study emphasizes the potential role of miRNAs in male infertility and provides a general overview for future studies aiming to find robust molecular markers for this condition.

Interplay between microRNAs and Wnt, transforming growth factor-ß, and bone morphogenic protein signaling pathways promote osteoblastic differentiation of mesenchymal stem cells.

Osteoblasts are terminally differentiated cells with mesenchymal origins, known to possess pivotal roles in sustaining bone microstructure and homeostasis. These cells are implicated in the pathophysiology of various bone disorders, especially osteoporosis. Over the last few decades, strategies to impede bone resorption, principally by bisphosphonates, have been mainstay of treatment of osteoporosis; however, in recent years more attention has been drawn on bone-forming approaches for managing osteoporosis. MicroRNAs (miRNAs) are a broad category of noncoding short sequence RNA fragments that posttranscriptionally regulate the expression of diverse functional and structural genes in a negative manner. An accumulating body of evidence signifies that miRNAs direct mesenchymal stem cells toward osteoblast differentiation and bone formation through bone morphogenic protein, transforming growth factor-ß, and Wnt signaling pathways. MiRNAs are regarded as excellent future therapeutic candidates because of their small size and ease of delivery into the cells. Considering their novel therapeutic significance, this review discusses the main miRNAs contributing to the anabolic aspects of bone formation and illustrates their interactions with corresponding signaling pathways involved in osteoblastic differentiation.

Diagnostic biomarker and therapeutic target applications of miR-326 in cancers: A systematic review.

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR-326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR-326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR-326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA-326 expression has an important role in cancer conditions and other diseases.

Tumor suppressor microRNAs in lung cancer: An insight to signaling pathways and drug resistance.

Lung cancer (LC) is the second common cancer for both women and men all over the world. Unfortunately, the number of LC deaths is increasing rapidly each year so early diagnosis of LC can be lifesaving. MicroRNAs are involved in multiple processes, such as cell differentiation, transcription, inflammation, proliferation, cell signaling, and apoptosis. In LC, microRNAs function as tumor suppressors (TS) or oncogenes depending on the targets. Changes in microRNAs expression level are related to tumor initiation, progression, and metastasis. MicroRNAs can regulate gene expression and thus affect the activity status of different signaling pathways including AKT, JAK-STAT, MAPK, TGF-ß, WNT, and ERK signaling pathways. Positive or negative effects on drug resistance of LC are directly affected by microRNAs and their target genes. MicroRNAs can be beneficial in combination therapy with other drugs and chemotherapeutic agents for LC.

Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines.

BACKGROUND: Although there are multiple treatments for lung cancer, the death rate of this cancer remains high because of metastasis in earlier stages. So a novel treatment for overcoming metastasis is urgently needed. Overexpression of high-mobility group AT-hook 2 (HMGA2), a nonhistone chromosomal protein has been observed in metastatic cancers. So, we suggested that HMGA2 upregulation may play a critical role in treating lung cancer. METHODS: The A549 cells were transfected with specific HMGA2 small interfering RNA (siRNA) using transfection reagent. Relative HMGA2 and matrix metallopeptidase 1 (MMP1), C-X-C chemokine receptor type 4 (CXCR4), vimentin, and E-cadherin messenger RNA expression levels were measured by quantitative real-time polymerase chain reaction. To diagnose cytotoxic effect of HMGA2 siRNA and other components of transfection process, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied. The migration capacity after transfection with HMGA2 siRNA was detected by wound-healing assay. RESULTS: HMGA2 siRNA significantly reduced HMGA2 expression in a dose-dependent manner 48 hours after transfection. Expression levels of MMP1, vimentin, and CXCR4 were reduced, but E-cadherin level was not changed meaningfully. HMGA2 knockdown significantly reduced cell survival rate and also led to the inhibition of cell migration. CONCLUSIONS: Our results indicated that RNA interference by downregulation of HMGA2 gene expression and affecting downstream genes led to the inhibition of cell migration and proliferation. Therefore, HMGA2 siRNA might be an alternative treatment option for metastatic lung cancer.

The MicroRNA-326: Autoimmune diseases, diagnostic biomarker, and therapeutic target.

MicroRNAs (miRNAs) are uniquely regulated in healthy, inflamed, activated, cancerous, or other cells and tissues of a pathological state. Many studies confirm that immune dysregulation and autoimmune diseases with inflammation are correlated with various miRNA expression changes in targeted tissues and cells in innate or adaptive immunity. In this review, we will explain the history and classification of epigenetic changes. Next, we will describe the role of miRNAs changes, especially mir-326 in autoimmunity, autoinflammatory, and other pathological conditions. A systematic search of MEDLINE, Embase, and Cochrane Library was presented for all related studies from 1899 to 2017 with restrictions in the English language. In recent years, researchers have concentrated on mostly those roles of miRNA that are correlated with the inflammatory and anti-inflammatory process. Latest studies have proposed a fundamental pathogenic role in cancers and autoinflammatory diseases. Studies have described the role of microRNAs in autoimmunity and autoinflammatory diseases, cancers, and so on. The miRNA-326 expression plays a significant role in autoimmune and other types of diseases.

Hypermethylation of IL-10 gene is responsible for its low mRNA expression in Behçet's disease.

Interleukin-10 (IL-10), produced generally by monocyte, T helper type 2 (Th2), and regulatory T cells (Treg), plays a central role in controlling inflammatory responses and regulating the immune response of the IL-10 mRNA expression. It is significantly down-regulated in many autoimmune diseases such as Behçet's disease; this is mostly associated with more aggressive complications. Nevertheless, the essential molecular process for its low expression has not been completely realized. The aim of this project was attempted to estimate the gene expression, promoter methylation, and protein levels to IL-10's down-regulated expression. In this study, blood samples from 51 (4 missed) patients and 63 (2 missed) healthy controls were taken, with the mononuclear cells isolated by the Ficoll Protocol. DNA and RNA were then subsequently extracted. Promoter methylation levels were evaluated by MeDIP-qPCR. Following this, the extracted RNA was converted to cDNA using the RT-PCR method, with the expression of IL-10 later evaluated by Real-time PCR. And then, serum levels of IL-10 were measured using ELISA method. As we expected, the expression level of the IL-10 gene was seen to significantly decline in the patient group in comparison to the control. Also, the rate of promoter methylation was significantly higher in the IL-10 mRNA low expression group (patient group) compared to its high expression group (healthy group) (P < 0.001). We revealed that hypermethylation of promoter region was the principal defect for the IL-10 mRNA low expression in patients with Behçet's disease.

Analysis of miRNA-221 Expression Level in Tumors and Marginal Biopsies from Patients with Breast Cancer (Cross-Sectional Observational Study).

BACKGROUND: miRNA-221 and miRNA-222 are two homologous microRNAs, the high-expression levels of which have been commonly demonstrated in the most current human cancer types as well as breast cancer. The purpose of this research was to determine the clinical value of measuring the expression level of hsa-miR-221-3p in breast cancer tissues and evaluate its biological and prognostic importance in breast cancer (BC). METHODS: A total of 40 tumor samples and matched tumor-free margin specimens were obtained during surgery from patients with BC. After total RNA extraction and cDNA synthesis, the relative expression level of hsa-miR221-3p in tumor and marginal tissues was examined by quantitative real-time PCR. Moreover, the association between hsa-miR-221-3p expression and clinicopathological features of patients was detected. RESULTS: The relative expression level of hsa-miR-221-3p in BC tissues was significantly higher than that in adjacent noncancerous breast biopsies (p ≤ 0.0001). Also, there was no significant association between hsa-miR-221-3p expression with clinicopathological characteristics (p > 0.05). The receiver operating characteristic (ROC) curve analyses also represented an optimum cutoff point of < 4.34 to show that hsa-miR-221-3p is an effective molecular biomarker for BC diagnosis. CONCLUSIONS: This study illustrated that analysis of hsa-miR-221-3p relative gene expression may be applied as a biomarker for screening BC patients and could be a substantial tool in diagnosis and prognosis. Also, that could be advantageous in decreasing surgical mistakes in tumor elimination through the surgery and enhancing all over the progression of surgery with reformed tumor clearance.

Expression Analysis of MicroRNA-222 in Breast Cancer.

BACKGROUND: miR-221 and miR-222 are homologous miRNAs located in tandem, within 1 kb from each other, on human x chromosome. Recent studies declared that microRNA-222 is aberrantly expressed in various malignancies. The goal of this research was to measure the expression level of has-miR-222-3P and reveal its diagnostic and prognostic importance in breast malignancy. METHODS: In this study, 40 pairs of cancerous and matched adjacent non-cancerous breast tissue were collected from patients, and real-time PCR was used to measure the relative expression of miR-222. RESULTS: Our study clarified that microRNA-222 is enhanced in tumor tissues in comparison with normal tissue margins (p ≤ 0.05) and overexpression of miR-222 was not associated with clinicopathological factors such as age, BMI, menopausal status, histological type, grade, stage, tumor size, lymph node metastasis (p > 0.05). The receiver operating characteristic (ROC) curve analysis displayed an optimum cutoff point of < 4.17 to prove that miR-222 is a useful biomarker in breast cancer diagnosis. CONCLUSIONS: Our findings on miR-222 suggest that it could be a potentially useful target for control and management of breast malignancy.

Expression Patterns of CXCL12 and its Receptor in Colorectal Carcinoma.

BACKGROUND: Stromal cell-derived factor-1 (also called CXCL12) and its receptor, CXCR4, have a key role in the pathogenesis and tumorigenesis of various cancers. The aims of the current study were to quantitatively examine the expression of CXCR4 and CXCL12 genes in colorectal cancer and to correlate their expression degree with clinicopathological features. METHODS: Tumor tissue samples were collected from 47 patients with CRC. Total RNA was isolated from resection tissues and real-time PCR analysis was performed to examine mRNA levels of CXCL12 and CXCR4 genes. RESULTS: No significant differences were observed for both CXCL12 and CXCR4 between tumor tissues and the adjacent non-affected tissues, although a borderline significant correlation (p = 0.052) were detected between gene expression of CXCL12 and CXCR4 in tumor tissues. Our results also indicated that there was no significant correlation between expression pattern of CXCL12/CXCR4 and clinicopathological variables. CONCLUSIONS: Our data showed that CXCL12 and CXCR4 are expressed simultaneously in colorectal carcinoma tissues, suggesting that expression of these chemokines and corresponding receptors may play a pivotal role in colorectal tumorigenesis, although it cannot be as a predictive factor for disease progression.

The potential role of toll-like receptor 4 Asp299Gly polymorphism and its association with recurrent cystic echinococcosis in postoperative patients.

The study of pathogenesis mechanisms of larval stages in the Taeniidae has recently focused on host genetic factors, particularly toll-like receptor (TLR) variations. However, the potential role of TLR4 polymorphism in hydatidosis has not yet been sufficiently elucidated in postoperative patients. In this case-control investigation, 80 patients from Iran, including 40 with acute hydatidosis (AH) and 40 with recurrent hydatidosis (RH), and 80 ethnically matched controls were evaluated from February 2015 to February 2017. Hydatidosis patients were confirmed using radiological, immunological, and histopathological examinations. Genotyping of Asp299Gly and Thr399Ile of TLR4 single-nucleotide polymorphisms was determined by restriction fragment length polymorphism, sequencing, and phylogenetic strategies. The heterozygous mutant-type TLR4 Asp299Gly genotype indicated a tendency to be associated with the occurrence of RH (P = 0.060) and conferred a 3-fold risk for susceptibility. There was no difference in genotype frequency of Asp299Gly between patients with AH and healthy controls (P = 0.42; OR, 1.82; 95% CI, 0.11-30.1%). Interestingly, a frequency of the G allele (12%: Gly) was observed to be a risk factor for susceptibility to RH patients (P = 0.050; OR, 7.08; 95% CI, 0.97-51.5%). A relative genetic variability of TLR4 Asp299Gly was found in RH patients (haplotype diversity: 0.700) compared to AH patients and healthy controls (Hd: 0.000). The Asp299Gly genotype was dominantly identified in patients with hepatic hydatid cysts. The TLR4 Thr399Ile codon was not detected except in a patient with a pulmonary hydatid cyst. The current findings enhance our knowledge regarding the TLR4 Asp299Gly polymorphism potentially leading to the development of RH, by skewing the immune system towards a Th2 response. Identification of the Asp299Gly codon may be a diagnostic hallmark in RH patients who have undergone unsuccessful postoperative intervention. However, further studies with a higher case number are needed on ethnic population from various geographic regions, in order to confirm this hypothesis.

Molecular analysis of more than 140 gene fusion variants and aberrant activation of EVI1 and TLX1 in hematological malignancies.

Gene fusions are observed in abnormal chromosomal rearrangements such as translocations in hematopoietic malignancies, especially leukemia subtypes. Hence, it is critical to obtain correct information about these rearrangements in order to apply proper treatment techniques. To identify abnormal molecular changes in patients with leukemia, we developed a multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) protocol and investigated more than 140 gene fusions resulting from variations of 29 prevalent chromosomal rearrangements along with EVI1 and TLX1 oncogenic expression in the presence of optimized primers. The potential of the MRT-PCR method was approved by evaluating the available cell lines as positive control and confirmed by sequencing. Samples from 53 patients afflicted with hematopoiesis malignancies were analyzed. Results revealed at least one chromosomal rearrangement in 69% of acute myeloid leukemia subjects, 64% of acute lymphoblastic leukemia subjects, and 81% of chronic myeloid leukemia subjects, as well as a subject with hypereosinophilic syndrome. Also, five novel fusion variants were detected. Results of this study also showed that chromosomal rearrangements, both alone and in conjunction with other rearrangements, are involved in leukemogenesis. Moreover, it was found that EVI1 is a suitable hallmark for hematopoietic malignancies.

Analysis of the Association between MDM4 rs4245739 Single Nucleotide Polymorphism and Breast Cancer Susceptibility.

BACKGROUND: MDM4 is a negative regulator of the p53 tumor suppression pathway. Recent studies have revealed that the rs4245739 A>C polymorphism of MDM4 in the 3-untranslated region makes it a miR-191 target site which leads to lower MDM4 expression. This study is aimed to detect if rs4245739 single nucleotide polymorphism (SNP) of the MDM4 gene influences the breast cancer development in Iranian-Azeri women. METHODS: Blood samples were taken from 260 healthy controls and 220 breast cancer women with ethnicity of Iranian-Azeri. Genotyping was done using Tetra-ARMS PCR. RESULTS: Alleles of MDM4 rs4245739 SNP had no significant different frequency between patients and controls (p > 0.05). Additionally, genotypes of MDM4 rs4245739 SNP did not increase or decrease breast cancer risk in patients when compared to healthy women. Also, there was no significant association between the alleles of MDM4 rs4245739 SNP and clinicopathological factors (p > 0.05). CONCLUSIONS: Considering the lack of association between MDM4 rs4245739 polymorphism and breast cancer, rs4245739 polymorphism of this gene seems to have no significant role in the pathophysiology of the disease.