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Background: Breast cancer is the most frequent malignancy in women worldwide and occurs when cells in the breast begin to grow out of control. Matrix metalloproteinases (MMP), including MMP1 protein, are important in the progression of various types of cancer. Quinacrine, a derivative of 9-aminoacridine, has been shown to inhibit the growth of several types of cancer cells. In this study, we examined the effect of Quinacrine on MMP1 gene expression in breast cancer cell lines MDA-MB 231 and MCF7. MDA-MB 231 cell line has triple negative breast cancer cells properties. Materials and Methods: Breast cancer cell lines, MDA-MB 231 and MCF7, were treated with 0.5 µM Quinacrine for 3 days. The dose was selected using MTT assay. Expression of MMP1 gene was quantified by Real-time PCR. Significance of observations were statistically checked by t-test using P

Mojdeh Akbari,1 Fakhrolmolouk Yassaee,2 Mona Aminbeidokhti,1 Atieh Abedin-Do,1,3 Reza Mirfakhraie1,41Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Obstetrics and Gynecology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3GREB, Dental Faculty, Department of Regenerative Medicine, Faculty of Medicine, Laval University, Quebec, Canada; 4Department of Molecular Genetics, Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Reza MirfakhraieDepartment of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar St, Velenjak Ave, Chamran highway, Tehran 19395-4719, IranTel/Fax +98 212 387 2572Email reza_mirfakhraie@yahoo.comFakhrolmolouk YassaeeDepartment of Obstetrics and Gynecology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, PO Box 1985717413, Tehran, IranEmail Dr_fyass@yahoo.comBackground: Uterine leiomyomas (ULMs) are benign uterine tumors that are estrogen-dependent. Recent studies suggest that the abnormal expression of the steroid receptor RNA activator 1 (SRA1) long non-coding RNA (lncRNA) might participate in the mechanisms of tumorigenesis of some hormone-dependent tumors including breast cancer. SRA1 is known to enhance the transcriptional activity of steroid receptors and also promotes steroidogenesis. The level of steroid hormones, such as estrogen and the progesterone, and their receptors play an important role in the development and growth of leiomyoma. The aim of the present study was to determine the expression level of lncRNA SRA1 in ULM tissues considering the MED12 mutation pattern.Methods: Mutation screening was performed for MED12 exons 1 and 2 and the intronic flanking regions using Sanger sequencing in 60 ULM tissues. Quantitative real-time polymerase chain reaction (qRT-PCRs) was performed in order to estimate the expression of lncRNA SRA1 in leiomyoma samples with and without MED12 gene mutations. The expression results were analyzed by using LinReg and REST software.Results: Mutations were detected in exon 2 of the MED12 in 28 (46.67%) ULM samples; including, 21 (75%) missense mutations and 7 (25%) in-frame deletions. No mutation was detected in the MED12 exon 1. LncRNA SRA1 was over-expressed in ULM samples without MED12 mutation compared with ULM samples harboring MED12 mutation (Expression ratio=2.5, P-value=0.004).Conclusion: Present results suggest that lncRNA SRA1 may explain the phenotypic difference observed in the tumor size of ULM samples considering MED12 mutation pattern. Therefore, it serves as a good therapeutic target and provides new insight into understanding the disease molecular mechanism.Keywords: MED12, mutation, SRA1, lncRNA, uterine leiomyoma

Maryam Khani,1 Jalil Hosseini,2 Reza Mirfakhraie,1 Mohsen Habibi,3 Eznollah Azargashb,4 Farkhondeh Pouresmaeili1,21Medical Genetics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Infertility and Reproductive Health Research Center (IRHRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Central laboratory, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Community Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranIntroduction: Prostate cancer (PCa) is the most common cancer among men and the second cause of cancer death among men. For early detection and differentiating PCa from benign prostate hyperplasia (BPH) tissue biopsy has been used for decades. However, circulating cell-free DNA (ccfDNA) testing is a noninvasive, fast, easily repeatable, and sensitive liquid biopsy for cancer detection. Hence, we aimed to investigate the value of the ccfDNA concentration and integrity index in peripheral blood of a population of Iranian prostatic patients for early diagnosis of the disease.Materials and methods: 100 subjects including 30 PCa, 40 BPH, and 30 healthy individuals were selected. ccfDNA was extracted from fresh blood plasma, and its total concentration and the integrity index were estimated by amplification of ALU115 and ALU247 repeat elements using quantitative real-time PCR.Results: In the PCa group, the ccfDNA concentration and its integrity were significantly higher than that of the BPH and healthy groups (P-value

Mahnaz Seifi-Alan,1 Roshanak Shams,1 Mojgan Bandehpour,2 Reza Mirfakhraie,1 Soudeh Ghafouri-Fard1 1Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Purpose: Neuropilin-1 (NRP1) as an isoform-specific receptor for vascular endothelial growth factor and placenta growth factor in endothelial cells has been demonstrated to be expressed in breast cancer cells where it plays functional roles in cell survival, invasion, and migration. We hypothesized that an expression of NRP1 in breast cancer tissues is associated with clinicopathological data of patients and expression of the tumor suppressor miR-206. Patients and methods: We evaluated the expression of NRP1 in 48 invasive ductal carcinomas of the breast and their corresponding adjacent noncancerous tissues (ANCTs) by means of real-time polymerase chain reaction. We also extracted data on miR-206 gene expression from the same cohort of patients to evaluate the correlation between expression levels of miR-206 and NRP1. In addition, we quantified NRP1 protein levels using the enzyme-linked immunosorbent assay technique. Results: No significant difference was found in NRP1 expression between tumoral tissues and ANCTs. We also assessed the associations between expression levels of NRP1 and clinicopathological data of patients and found no significant associations between NRP1 transcript levels and any characteristic. However, NRP1 protein concentrations were significantly higher in patients with lymph node involvement compared with those without lymph node involvement. No correlation was found between NRP1 and miR-206 expression levels. Conclusion: NRP1 protein levels might be an indicator of metastasis potential in breast cancer. Future studies are needed to confirm these results in larger cohorts of patients. Keywords: NRP1, neuropilin-1, breast cancer

Mohaddeseh Salehi,1,* Mona Amin-Beidokhti,2,* Behnam Safarpour Lima,3 Milad Gholami,2 Gholam-Reza Javadi,1 Reza Mirfakhraie2,4 1Department of Biology, Islamic Azad University, Science and Research Branch, 2Department of Medical Genetics, 3Department of Neurology, School of Medicine, 4Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Introduction: Migraine is a painful complex neurovascular disease characterized by recurrent moderate-to-severe headaches. Increased level of homocysteine is related to dilation of cerebral vessels and endothelial injury that could trigger migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine metabolism and, therefore, play an important role in the etiology of the disease. Objectives: We aimed to investigate the possible association between MTHFR gene rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian population. Methods: In this genetic association study, 498 individuals were enrolled, including 223 migraine patients and 275 healthy controls. Genotyping was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction fragment length polymorphism for C677T and A1298C polymorphisms. Results: The association between rs4846049 and C677T polymorphisms and migraine was observed. For the rs4846049 polymorphism, the association was detected under a dominant model (P=0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41–0.87), and for the C677T polymorphism, the TT genotype frequency was significantly different in the studied groups (P=0.009; OR =2.48; 95% CI, 1.25–4.92). No significant differences in the genotype or allele frequencies were found for the A1298C polymorphism between the migraineurs and controls. Conclusion: Present data provide evidence for the association of rs4846049 and C677T polymorphisms in the MTHFR gene and migraine. Further studies are required to validate the significance of the studied genetic variations in diverse ethnic populations. Keywords: migraine, genetic association study, MTHFR, single nucleotide polymorphism

In brief, we report an Iranian family with a history of both azoospermia and premature ovarian insufficiency with the same heterozygote mutation in the NR5A1 gene that can be transmitted. As far as we know, this is the first observation that a common mutation in NR5A1 can cause these above-mentioned phenotypes in a family. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors cause about 10% of male infertility. However, the etiology of the majority of male infertility cases including non-obstructive azoospermia or severe oligospermia remains idiopathic. Defects in DNA repair during spermatogenesis are thought to underlie some types of testicular failure. Evidence is accumulating to demonstrate the importance of DNA repair defects in human non-obstructive azoospermia. In eukaryotes, homologs of the bacterial MutL proteins, including MLH3, function in DNA mismatch repair and recombination pathway and therefore may play a crucial role in spermatogenesis. Materials and Methods: In the present study, we investigated the association between C2531T polymorphism in the MLH3 gene non-obstructive azoospermia using the tetra-amplification refractory mutation system-PCR (4P-ARMS-PCR) method in 94 non-obstructive azoospermia patients and 80 fertile controls. The amplified DNA was visualized on 2.0% agarose gel containing DNA safe viewer. Results: We observed an increased risk of male infertility associated with the MLH3 (CT+TT) (OR, 2.34; 95% CI, 1.19-4.62; p=0.012) genotype, compared to the MLH3 CC genotype. Conclusion: Our results show an association between C2531T polymorphism in MLH3 with non-obstructive azoospermia. Therefore, the MLH3 polymorphism may be genetic determinants for human spermatogenesis impairment. [ABSTRACT FROM AUTHOR]