Papers by Maryam Zanjirband
Scientific reports, Mar 14, 2024
Long non-coding RNA (lncRNA) regulates many physiological processes by acting as competitive endo... more Long non-coding RNA (lncRNA) regulates many physiological processes by acting as competitive endogenous RNA (ceRNA). The dysregulation of lncRNA X-inactive specific transcript (XIST) has been shown in various human disorders. However, its role in the pathogenesis of polycystic ovary syndrome (PCOS) is yet to be explored. This study aimed to explore the underlying mechanism of XIST in the pathogenesis of PCOS, specifically through dataset functional analysis. GEO PCOS datasets including RNA-seq, microarray, and miRNA-seq in granulosa cells (GCs) and blood, were examined and comprehensively analyzed. Enrichment analysis, ROC curve constructions, lncRNA-miRNA-mRNA interaction network analyses, and qRT-PCR validation were performed followed by a series of drug signature screenings. Our results revealed significant dysregulation in the expression of 1131 mRNAs, 30 miRNAs, and XIST in GCs of PCOS patients compared to healthy individuals. Of the120 XIST-correlated upregulated genes, 25 were enriched in inflammation-related pathways. Additionally, 5 miRNAs were identified as negative regulators of XIST-correlated genes. Accordingly, a ceRNA network containing XIST-miRNAs-mRNAs interactions was constructed. Furthermore, 6 genes, including AQP9, ETS2, PLAU, PLEK, SOCS3, and TNFRSF1B served as both GCs and bloodbased biomarkers. By analyzing the number of interactions among XIST, miRNAs, and mRNAs, we pinpointed ETS2 as the pivotal gene within the ceRNA network. Our findings reveal a novel XISThsa-miR-146a-5p, hsa-miR-144-3p, and hsa-miR-1271-5p-ETS2 axis that comprehensively elucidates the XIST-associated mechanism underlying PCOS onset. qRT-PCR analysis further confirmed the, overexpression of both XIST and ETS2. Furthermore, our results demonstrated that XIST and ETS2 were correlated with some assisted reproductive technologies outcomes. Finally, we identified two novel compounds including, methotrexate/folate and threonine using drug-gene interaction databases for PCOS management. These findings provide novel insights into the molecular etiology, diagnosis, and potential therapeutic interventions for PCOS.
Cancer Drug Resistance, 2023
Aim: Given the encouraging results of the p53-Mdm2 inhibitor RG7388 in clinical trials and the vi... more Aim: Given the encouraging results of the p53-Mdm2 inhibitor RG7388 in clinical trials and the vital function of miR-16-5p in suppressing cell proliferation, the aim of the present study was to investigate the combined impact of RG7388 and miR-16-5p overexpression on the childhood acute lymphoblastic leukemia (chALL). Methods: miRTarBase and miRDB, along with KEGG and STRING databases, were used to predict miR-16-5p target genes and explore protein-protein interaction networks, respectively. B- and T-lymphoblastic cell lines, in addition to patient primary cells, were treated with RG7388. Ectopic overexpression of miR-16-5p in Nalm6 cell line was induced through cell electroporation and transfection of microRNA mimics was confirmed by qRT-PCR. Cell viability was evaluated using the MTT assay. Western blot analyses were performed to evaluate the effects of RG7388 and miR-16-5p upregulation on the protein levels of p53 and its downstream target genes in chALL cells. Paired sample t-te...
Cancer Research, 2017
Background The tumor suppressor p53 is a central hub in molecular signaling pathways that control... more Background The tumor suppressor p53 is a central hub in molecular signaling pathways that control the integrity of the human genome. The p53 protein functions as a transcription factor and increases the expression of many cellular genes which contribute to activation of cell cycle arrest, apoptosis and DNA repair. MDM2 is another important p53 target gene, and the MDM2 protein is capable of binding directly to p53 and directing it for degradation through the ubiquitin-dependent proteolytic pathway. Inhibition of MDM2 stabilizes p53 and MDM2 inhibitors are being explored clinically as therapies. Stabilization alone may not be enough to increase the activity of p53, and posttranslational modification of p53 by phosphorylation has been proposed to be an important contributory mechanism by which p53 becomes functionally active. Therefore maintaining the phosphorylated status of p53 in tumor cells may help to enhance its growth inhibitory and pro-apoptotic role. Wild type p53 – induced p...
Annals of Oncology, 2020
Methods: CuO NPs (80AE20 nm as determined by dynamic light scattering) were synthesized by the pr... more Methods: CuO NPs (80AE20 nm as determined by dynamic light scattering) were synthesized by the precipitation method. Intracellular accumulation of CuO NPs was measured by atomic absorption spectroscopy. The panel of cell lines included HCT116 colon and MDA-MB-231 triple-negative breast carcinomas as well as K562 (CML) cell line and its multidrug-resistant K562/4 subline. The cytotoxicity of CuO NPs, NAC and their combination were determined in MTT assays. Flow cytometry was used to analyze the mechanisms of cell response. Caspase-3 and poly(ADPribose) polymerase (PARP) were detected by immunoblotting. Results: CuO NPs showed a slight toxicity for all tested cell lines after 72 h, while in combination with the non-toxic NAC a rapid (within 2 h) ROS generation and cell death by 8 h were detected. CuO NPs weakly accumulated in the cells, so ROS generation is likely to occur mainly outside the cells. The IC 50 of the combination was 2-3 orders of magnitude smaller compared to NPs alone. Death associated events differed between the cell lines but generally caspase-independent apoptosis was followed by irreversible damage of the plasma membrane. Importantly, the combination of CuO NPs with NAC was equally potent for K562 cells and the multidrugresistant K562/4 subline. Reduction of Cu 2+ to Cu + upon interaction with the thiol group in NAC can trigger ROS formation. Conclusions: The combination of CuO NPs and NAC killed human tumor cell lines including the multidrug-resistant variant. Rapid ROS generation can be promising in situations where tumor cells acquire multidrug resistance during treatment. Also, engineering of supramolecular systems will allow to guide copper to critical cysteine residues in specific proteins for their oxidative destruction.
Frontiers in Clinical Drug Research - Anti-Cancer Agents: Volume 8, 2021
Taxonomy and Biosystematics Journal, 2010
Micro organisms that grow in habitats characterized by high or low temperatures, acidic or alkali... more Micro organisms that grow in habitats characterized by high or low temperatures, acidic or alkaline pHs, high salt concentrations and high pressures have been termed extremophiles. The halophilic microorganisms are a group of extremophiles that are able to grow in the presence of NaCl. For isolation of moderately halophilic bacteria, specimens were collected from sea water (Persian Gulf) and different parts of tannery factory. Samples were enriched in specific medium for halophils, and bacteria were purred with streak plate method and were identified. To investigate the effects of various temperatures and various pH on their growth, drop plate method and microtitre plate method were used. In this study, 8 bacteria from different parts of tannery factory and 8 bacteria from Persian Gulf were isolated. Phenotypic and biotipic studies were accomplished the collected bacteria. Results indicated that, the best temperature for tannery factory and Persian Gulf isolates were 28C and 37C r...
Iranian Journal of Biotechnology, 2008
Tetrahydro-2-methyl-4-pyrimidine carboxylic acid (ectoine) is an excellent osmoprotectant. Ectoin... more Tetrahydro-2-methyl-4-pyrimidine carboxylic acid (ectoine) is an excellent osmoprotectant. Ectoine and hydroxyl ectoines are of great significance to the biotechnology industry, thus the detection and isolation of ectoine producing bacteria is of great importance. Hence, this study involved the detection of the ectC gene (encoding ectoin synthase enzyme) using poly- merase chain reaction (PCR) method. For isolation of moderately halophilic bacteria, environmental samples were collected from various sites of a tannery factory in Isfahan, and the Persian Gulf. A synthetic broth medium was used and the optimum concentration of salt (NaCl) was determined by the microtitre plate method. Based on the alignment of relevant ectC gene sequences available in the GenBank which included sequences from 24 validly described Halomonas species, putative genus-specific primers were designed. Primers were designed in such a way to amplify a 277bp region of the ectC gene in the putative Halomonas stra...
Taxonomy and Biosystematics, 2010
Current Drug Targets
MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a... more MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a low level in normal cells. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies with wild-type TP53, p53 function is inhibited through other mechanisms. Recently, synthetic small molecule inhibitors have been developed which target a small hydrophobic pocket on MDM2 to which p53 normally binds. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field. It emphasizes on the p53 function, regulation of p53, targeting of the p53-MDM2 interaction for cancer therapy, and p53-dependent and -independent effects of inhibition of p53-MDM2 interaction. Then, representatives of small molecule MDM2-p53 binding antagonists are introduced with a focus on those entered into clinica...
Cancer medicine, 2018
NUCOLL43 is a novel ovarian clear cell carcinoma (O-CCC) cell line that arose from a primary cult... more NUCOLL43 is a novel ovarian clear cell carcinoma (O-CCC) cell line that arose from a primary culture of a patient's malignant ascites. The cells grow reliably in cell culture with a doubling time of approx. 45 hours and form colonies at high efficiency. They have a very high degree of loss of heterozygosity (LOH) affecting approximately 85% of the genome, mostly copy neutral and almost identical to the original tumor. The cells express epithelial (pan-cytokeratin) and mesenchymal (vimentin) characteristics, CA125 and p16, like the original tumor. They also express ARID1A but not HNF-1β and, like the original tumor, and are negative for p53 expression, with no evidence of p53 function. NUCOLL43 cells express all other DNA damage response proteins investigated and have functional homologous recombination DNA repair. They are insensitive to cisplatin, the PARP inhibitor rucaparib, and MDM2 inhibitors but are sensitive to camptothecin, paclitaxel, and NVP-BEZ235. The NUCOLL43 cell l...
Iranian Journal of Biotechnology, Jul 1, 2008
Taxonomy and Biosystematics, Jan 15, 2010
Journal of Biotechnology, 2010
Journal of Biotechnology, 2010
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Papers by Maryam Zanjirband