Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
Aberrant Expression of Immune-related MicroRNAs in Pediatric Patients with Asthma
246
254
EN
Hala Gouda
Elnady
Department of Child Health, Medical Research Division, National Research Center, Egypt.
Lobna Sayed
Sherif
Department of Child Health, Medical Research Division, National Research Center, Egypt.
Naglaa Mohamed
Kholoussi
Immunogenetics Department, Human Genetics and Genome Research Division, National Resrearch Center, Egypt.
Mona Ali
Azzam
Department of Pediatrics, Faculty of Medicine, Suez Canal University, Egypt; McMaster University, Hamilton, Canada.
Ahmed Rashad
Foda
Department of Child Health, Medical Research Division, National Research Center, Egypt.
Iman
Helwa
Immunogenetics Department, Human Genetics and Genome Research Division, National Resrearch Center, Egypt.
Rania Nabil
Sabry
Department of Child Health, Medical Research Division, National Research Center, Egypt.
Eman
Eissa
Immunogenetics Department, Human Genetics and Genome Research Division, National Resrearch Center, Egypt.
Reham Faisal
Fahmy
Department of Child Health, Medical Research Division, National Research Center, Egypt.
MicroRNAs (miRNAs) have been implicated as regulatory molecules that could play a considerable role in the pathogenesis of different diseases including asthma. This work aims at exploring the role of miR-146a and miR-106b in the pathogenesis of asthma and their association with asthma severity, IgE, and inflammatory cytokines in asthmatic children. Thirty asthmatic children and twenty age-matched healthy children aged 4-17 years old were enrolled. Expression of plasma miR-146a and miR-106b was measured using quantitative real-time PCR. Plasma levels of interleukin-5 (IL-5) and interleukin-13 (IL-13) were assessed using ELISA. Lung functions were measured by Spirometry. MiR-146a and miR-106b were significantly over-expressed in asthmatic children compared to healthy children. A significant positive correlation between total IgE and both miR-146a and miR-106b was found while no significant correlation could be detected between these miRNAs and asthma severity in asthmatic children. Plasma levels of IL-5 and IL-13 were non-significantly higher in asthmatic children compared to healthy children, and there was no significant correlation between them and both miR-146a and miR-106b expressions in the asthmatic children. The aberrant expression of immune-related miRNAs (miR-146a and miR-106b) and inflammatory cytokines (IL-5 and IL-13) among asthmatic children suggest their probable role in asthma pathogenesis.
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
Association of Pathogenic Missense and Nonsense Mutations in Mitochondrial COII Gene with Familial Adenomatous Polyposis (FAP)
255
265
EN
Zahra
Shaker Ardakani
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Mohammad Mehdi
Heidari
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Mehri
Khatami
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.
Morteza
Bitaraf Sani
Animal Science Research Department, Yazd Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education & Extension Organization (AREEO), Yazd, Iran.
Nuclear genetic mutations have been extensively investigated in solid tumors. However, the role of the mitochondrial genome remains uncertain. Since the metabolism of solid tumors is associated with aerobic glycolysis and high lactate production, tumors may have mitochondrial dysfunctions. Familial adenomatous polyposis (FAP) is a rare form of colorectal cancer and an autosomal dominant inherited condition that is characterized by the progress of numerous adenomatous polyps in the rectum and colon. The present study aimed at understanding the nature and effect of mitochondrial cytochrome c oxidase subunit 2 (COII) gene mutations in FAP tumorigenesis. Fifty-six (26 familial and 30 sporadic) FAP patients and 60 normal controls were enrolled in this study. COII point mutations were evaluated by PCR and direct sequencing methods, and a total of 7 mtDNA mutations were detected (3 missense, 1 nonsense, and 3 synonymous variations). Novel non-synonymous COII gene mutations were mostly in heteroplasmic state. These mutations change amino acid residues in the N-terminal and C-terminal regions of COXII. Bioinformatics analysis and three-dimensional structural modeling predicted that these missense and nonsense mutations have functional importance, and mainly affected on cytochrome c oxidase (complex IV). Also, FAP patients carried a meaningfully higher prevalence of mutations in the COII gene in comparison with healthy controls (P <0.001). Analysis of cancer-associated mtDNA mutation could be an invaluable tool for molecular assessment of FAP so that these findings can be helpful for the development of potential new biomarkers in the diagnosis of cancer for future clinical assessments.
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
The Expression Pattern and Clinicopathological Importance of Hsa_circ_000425 in Colorectal Cancer
266
272
EN
Davood
Mohammadi
Department of Surgery, School of medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Ali
Bastani
Department of Internal Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Yazdan
Zafari
Department of Hematology and Medical Oncology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Sohrab
Esmeilazadeh
School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Nafiseh
Rastgoo
School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Mohammad
Bargahi
School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Sahar
Moghbelinejad
Research Institute for Prevention of Non-Communicable Diseases, Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran.
Although colorectal cancer (CRC) is one of the most common cancers, the exact molecular mechanism of this cancer is not yet known. Circular RNAs (circRNAs), a class of non-coding RNAs, are newly identified and their role in the pathogenesis of various cancers has been shown. In this research, we studied the expression pattern and clinical importance of hsa_circ_000425 in CRC patients. After evaluation of hsa_circ_000425 expression rate in 4 CRC cell lines and 100 paired CRC tissues, the potential correlation between hsa_circ_000425 expression rate and clinicopathological parameters of CRC patients was analyzed. Additionally, receiver operating characteristic (ROC) curve was drawn to study the diagnostic value of hsa_circ_000425. A significant down regulation of hsa_circ_000425 was observed in both CRC tissues and cell lines. In addition, this downregulation was significantly associated with differentiation and lymphatic metastasis. The area under the ROC curve of hsa_circ_000425 was 0.839 (P < 0.001). hsa_circ_000425 may have a role in the pathogenesis of CRC and might act as a potential biomarker for the diagnosis and treatment of CRC; although further molecular studies must be performed in this regard.
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
Downregulated Expression of WWOX in Cervical Carcinoma: A Case-Control Study
273
287
EN
Shikha
Srivastava
Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India.
Uday
Pratap Shahi
Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Arti
Divya
Indian Railways Cancer Institute and Research Centre, Varanasi, India.
Sadhana
Gupta
Department of Obstetrics and Gynaecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Indu
Singh
Apollo Clinic, Mehmoorganj, Varanasi, India.
Jagat Kumar
Roy
Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University,Varanasi-221005, India.
Integration of human papilloma virus (HPV) in human genome is a random event, and fragile sites are one of the most susceptible sites for viral integrations. WWOX (WW-domain containing oxidoreductase) gene harbours the second most common fragile site, FRA16D, and can be an important candidate for HPV integration and cervical carcinogenesis. Our aim was to evaluate the potential role of WWOX in cervical carcinogenesis. Presence of HPV and its genotype was detected by PCR in normal cervix tissues and human cervical carcinoma. The expression of WWOX transcript and its protein was examined by RT-PCR, RNA in situ hybridization, and immunoblotting. Southern blotting and sequencing were used to determine the alternative transcripts of WWOX. Statistical analyses were performed by Mann Whitney U-test, Pearson correlation coefficient test at significance level of P value < 0.05. Prevalence of HPV was observed in cervicitis (40%), cervical intraepithelial neoplasia patients (50%), and invasive cervical carcinoma patients (89.6%). Clinicopathological findings suggested a correlation of reduced level of WWOX protein and progression of cervical carcinoma deciphering its role in tumorigenesis. Furthermore, we observed aberrant WWOX transcript having deleted exon 6-8 region in invasive cervical cancer tissues as well as normal cervix samples. More than 60% of cervical carcinoma samples showed reduced protein level with an increase in wild type transcript level suggesting the involvement of a negative regulator, pAck1 (activated Cdc42- associated kinase) which might ubiquitinate WWOX protein leading to its degradation. Also, nuclear retention of WWOX transcript in invasive cervical carcinoma tissues suggests its regulation at post-transcriptional level. Our findings suggest that WWOX acts as a tumor suppressor in cervical carcinoma and could act as a potential therapeutic target for the disease.
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
Monophosphoryl Lipid A and Retinoic Acid Combinations Increased Germ Cell Differentiation Markers Expression in Human Umbilical Cord-derived Mesenchymal Stromal Cells in an In vitro Ovine Acellular Testis Scaffold
288
295
EN
Ali
Shojaeian
Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Ameneh
Mehri-Ghahfarrokhi
Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Mehdi
Banitalebi-Dehkordi
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Infertility is known as one of the most common problems among couples. In this regard, generation of male germ cells from adult stem ones are among the current promising priorities of researchers. Mesenchymal stromal cells (MSCs) were previously induced to differentiate into germ-like progenitors in vitro. Monophosphoryl lipid A (MPLA) is a detoxified derivative of lipopolysaccharides (LPS) that lacks many of the endotoxic properties of LPS. Our present study aimed to investigate the expression of migration genes (CXCR4, VCAM1, VEGF, MMP2, and VLA4), and differentiation markers during human umbilical mesenchymal stromal cells (hUMSCs) culture in the presence of retinoic acid (RA) and MPLA-treated acellular testis. Accordingly, the high expression levels of deleted in azoospermia-like (DAZL), piwi-like RNA-mediated gene silencing 2 (PIWIL2) transcripts as well as protein were consequently observed in treated hUMSCs. It was concluded that combination treatment (i.e., MPLA/RA) had more prominent results than each of the treatments alone, even though MPLA and RA could be regarded as inducer of migration and differentiation, respectively. Ultimately, it was suggested to introduce the use of combination treatment as a more effective strategy to improve therapies in regenerative medicine.
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
Investigating Genetic Factors Contributing to Variable Expressivity of Class I 17p13.3 Microduplications
296
306
EN
Giovanna Cantini
Tolezano
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Silvia Souza da
Costa
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Marília de Oliveira
Scliar
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Walter Luis Magalhães
Fernandes
Department of Paediatrics, College of Medicine of Pouso Alegre, Pouso Alegre, MG, Brazil.
Paulo Alberto
Otto
Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Débora Romeo
Bertola
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Carla
Rosenberg
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Angela Maria
Vianna-Morgante
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
Ana Cristina Victorino
Krepischi
Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
17p13.3 microduplications are rare copy number variations (CNVs) associated with variable phenotypes, including facial dysmorphism, developmental delay, intellectual disability, and autism. Typically, when a recognized pathogenic CNV is identified, other genetic factors are not considered. We investigated via whole-exome sequencing the presence of additional variants in four carriers of class I 17p13.3 microduplications. A 730 kb 17p13.3 microduplication was identified in two half-brothers with intellectual disability, but not in a third affected half-brother or blood cells from their normal mother (Family A), thus leading to the hypothesis of maternal germline mosaicism. No additional pathogenic variants were detected in Family A. Two affected siblings carried maternally inherited 450 kb 17p13.3 microduplication (Family B); the three carriers of the microduplication exhibited microcephaly and learning disability/speech impairment of variable degrees. Exome analysis revealed a variant of uncertain significance in RORA, a gene already linked to autism, in the autistic boy; his sister was heterozygous for a CYP1B1 pathogenic variant that could be related to her congenital glaucoma. Besides, both siblings carried a loss-of-function variant in DIP2B, a candidate gene for intellectual disability, which was inherited from their father, who also exhibited learning disability in childhood. In conclusion, additional pathogenic variants were revealed in two affected carriers of class I 17p13.3 microduplication (Family B), probably adding to their phenotypes. These results provided new evidence regarding the contribution of RORA and DIP2B to neurocognitive deficits, and highlighted the importance of full genetic investigation in carriers of CNV syndromes with variable expressivity. Finally, we suggest that microcephaly may be a rare clinical feature also related to the presence of the class I 17p13.3 microduplication.
Babol University of Medical Sciences
International Journal of Molecular and Cellular Medicine (IJMCM)
2251-9637
9
4
2020
11
1
PD-1, TIM-3, and LAG-3 Expression in T Cells in a Patient with Recurrent Ossifying Fibroma: A Case Report
307
311
EN
Alejandro
García-Muñoz
Maxillofacial Surgery Service, Hospital Juárez de México, Mexico City, Mexico.
Nayeli Goreti
Nieto-Velázquez
Research División, Hospital Juárez de México, Mexico City, Mexico.
Gabriela
Damian-Morales
Research División, Hospital Juárez de México, Mexico City, Mexico.
Carlos
Liceaga-Escalera
Maxillofacial Surgery Service, Hospital Juárez de México, Mexico City, Mexico.
Luis Alberto
Montoya-Perez
Maxillofacial Surgery Service, Hospital Juárez de México, Mexico City, Mexico.
Madeleine
Cruz-Vélez
Maxillofacial Surgery Service, Hospital Juárez de México, Mexico City, Mexico.
Pabel Antonio
Gómez-Hernández
Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (FES-Iztacala UNAM), Estado de México, México.
Cynthia
Trejo-Iriarte
Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (FES-Iztacala UNAM), Estado de México, México.
Rodolfo
Pastelin-Palacios
Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, México.
Mario
Moreno-Eutimio
Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (FES-Iztacala UNAM), Estado de México, México.
Central ossifying fibroma is a benign, slow-growing tumor of mesenchymal origin with a predilection for the mandibular premolar and molar areas. The immunophenotype of T cells involved in the antitumor response against this benign tumor is unknown. In this case report, we described a case of a 48-year-old woman presenting with a very large recurrent ossifying fibroma in the mandible, which was successfully treated with hemimaxillectomy. In addition, we evaluated the expression of programmed cell death 1 receptor (PD-1), lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), CD69 (activation inducer molecule) and CD25 (α chain of the high-affinity IL-2 receptor) in T cell populations from the tumor and peripheral blood of this uncommon lesion. The patient presented recurrent ossifying fibroma, and the tumor-infiltrating and peripheral blood T cells showed expression of PD-1, LAG-3, and TIM-3, suggesting an exhausted T cell response.