Publications by authors named "Fatemeh Shamsabadi"

10 Publications

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Low expression of LncRNA-CAF attributed to the high expression of HIF1A in esophageal squamous cell carcinoma and gastric cancer patients.

Mol Biol Rep 2022 Jan 18. Epub 2022 Jan 18.

Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.

Purpose: Cancer-associated fibroblasts (CAFs) are major components of tumor microenvironment that stimulate ESCC and GC progression. The LncRNA-CAF, FLJ22447, is located in the vicinity of HIF1A, while their association remains unclear. This study aims to assess the FLJ22447 expression in the ESCC and GC patients and evaluate its association with the HIF1A gene.

Methods: Fresh ESCC and GC tumor samples and their adjacent non-tumor tissues were collected from patients who underwent surgery in Imam Khomeini Hospital, Tehran, Iran. The expression of FLJ22447, HIF1A, and VEGF was evaluated using qRT-PCR test. The association of their expression with tumor clinicopathological features in ESCC patients was assessed. System biology tools were then applied for the possible biological subsequences of the FLJ22447.

Results: A significant reduction in FLJ22447 expression was observed in ESCC and GC tissues than adjacent non-tumor tissues, while, the expression of HIF1A and VEGF were increased. Low expression of FLJ22447 was significantly correlated with HIF1A (P = 2.4e-73, R = 0.63) and VEGF (P = 0.00019, R = 0.15) expression. A significant relationship was detected between the high expression of HIF1A and tumor stages (I-II) and it was related to the reduced survival of ESCC patients. Conversely, increased VEGF expression was linked to the advanced stages (III-IV) and metastasis in ESCC. The analysis of FLJ22447-interacted proteins showed that MYC, JUN, SMRCA4, PPARG, AR, FOS, and CEBPA are the hub genes. These proteins were implicated in the cancer related pathways. Among them, SPI1, E2F1, TCF7L2, and STAT1 were significantly expressed in esophageal and gastric cancers that were functionally involved in the proliferation, apoptosis, and angiogenesis pathways in cancer.

Conclusion: The results suggested that FLJ22447 may have a regulatory function on the HIF1A expression. We identified the FLJ22447-interacted proteins and their molecular function in cancer pathogenesis. Further research emphasis is to realize the association of FLJ22447 with its protein partners in progression of cancer. These may provide an insight into the FLJ22447 activity that could introduce it as a potential value in tumor gene therapy.
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http://dx.doi.org/10.1007/s11033-021-06882-0DOI Listing
January 2022

In silico drug repurposing for the treatment of heart diseases using gene expression data and molecular docking techniques.

Biochem Biophys Res Commun 2021 10 5;572:138-144. Epub 2021 Aug 5.

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran; Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address:

Heart diseases are known as the most primary causes of mortality worldwide. Although many therapeutic approaches and medications are proposed for these diseases, the identification of novel therapeutics in fatal heart conditions is promptly demanded. Besides, the interplay between gene expression data and molecular docking provides several novel insights to discover more effective and specific drugs for the treatment of the diseases. This study aimed to discover potent therapeutic drugs in the heart diseases based on the expression profile of heart-specific genes exclusively. Initially, the heart-specific and highly expressed genes were identified by comparing the gene expression profile of different body tissues. Subsequently, the druggable-genes were identified using in silico techniques. The interaction between these druggable genes with more than 1600 FDA approved drugs was then investigated using the molecular docking simulation. By comprehensively analyzing RNA-sequencing data obtained from 949 normal tissue samples, 48 heart-specific genes were identified in both the heart development and function. Notably, of these, 24 heart-specific genes were capable to be considered as druggable genes, among which only MYBPC3, MYLK3, and SCN5A genes entered the molecular docking process due to their functions. Afterward, the pharmacokinetics properties of top 10 ligands with the highest binding affinity for these proteins were studied. Accordingly, methylergonovine, fosaprepitant, pralatrexate, daunorubicin, glecaprevir, digoxin, and venetoclax drugs were competent, in order to interact with the target proteins perfectly. It was shown that these medications can be used as specific drugs for the treatment of heart diseases after fulfilling further experiments in this regard.
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http://dx.doi.org/10.1016/j.bbrc.2021.07.076DOI Listing
October 2021

Identification of hub genes associated with RNAi-induced silencing of XIAP through targeted proteomics approach in MCF7 cells.

Cell Biosci 2020 11;10:78. Epub 2020 Jun 11.

Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Zip Code: 4934174515, Gorgan, Iran.

Background: The X-linked inhibitor of apoptosis protein (XIAP) is the most potent caspase inhibitor of the IAP family in apoptosis pathway. This study aims to identify the molecular targets of XIAP in human breast cancer cells exposed to XIAP siRNA by proteomics screening. The expression of XIAP was reduced in MCF-7 breast cancer cells by siRNA. Cell viability and the mRNA expression level of this gene were evaluated by MTS and quantitative real-time PCR procedures, respectively. Subsequently, the XIAP protein level was visualized by Western blotting and analyzed by two-dimensional (2D) electrophoresis and LC-ESI-MS/MS.

Results: Following XIAP silencing, cell proliferation was reduced in XIAP siRNA transfected cells. The mRNA transcription and protein expression of XIAP were decreased in cells exposed to XIAP siRNA than si-NEG. We identified 30 proteins that were regulated by XIAP, of which 27 down-regulated and 3 up-regulated. The most down-regulated proteins belonged to the Heat Shock Proteins family. They participate in cancer related processes including apoptosis and MAPK signaling pathway. Reduced expression of HSP90B1 was associated with apoptosis induction by androgen receptor and prostate specific antigen. Suppression of XIAP resulted in the enhancement of GDIB, ENO1, and CH60 proteins expression. The network analysis of XIAP-regulated proteins identified HSPA8, HSP90AA1, ENO1, and HSPA9 as key nodes in terms of degree and betweenness centrality methods.

Conclusions: These results suggested that XIAP may have a number of biological functions in a diverse set of non-apoptotic signaling pathways and may provide an insight into the biomedical significance of XIAP over-expression in MCF-7 cells.
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http://dx.doi.org/10.1186/s13578-020-00437-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291505PMC
June 2020

Proteomics evaluation of MDA-MB-231 breast cancer cells in response to RNAi-induced silencing of hPTTG.

Life Sci 2019 Dec 12;239:116873. Epub 2019 Sep 12.

Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran; AryaTinaGene Biopharmaceutical Company, Gorgan, Iran. Electronic address:

Aims: Breast cancer is the most common cancer in women worldwide. Several genes are up-regulated in breast cancer such as human pituitary tumor transforming gene (hPTTG). This study aims to evaluate cell proliferation and the downstream expression pattern of hPTTG1 gene at the mRNA and protein levels after specific down-regulation of hPTTG1 by siRNA.

Main Methods: The human breast cancer MDA-MB-231 cell line was transfected with siRNA against hPTTG1. The mRNA and protein expression levels were examined by Real-time PCR and Western blot, respectively. The cell proliferation was assayed by MTS. To investigate the pattern of protein expression, total cellular protein was analyzed by 2D gel electrophoresis and mass spectroscopy. Subsequently, the possible biological consequences were determined by the bioinformatics databases.

Key Findings: Subsequent of hPTTG1 silencing in the MDA_MB-231 cells, the proliferation of cells decreased obviously. In response to hPTTG1 silencing, the levels mRNA and protein were effectively down-regulated 80% and 50%, respectively, at 48 h post-transfection. The proteomics evidenced that PTTG1 increased the expression of 5 proteins. The reduced expression of PTTG1 was functionally involved in hypoxia (NPM1, ENO1), cell proliferation and apoptosis (ENO1, NPM1, NME1, STMN1), and metastasis (NPM1, NME1).

Significance: We identified the hPTTG1-regulated proteins and its molecular mechanism in pathogenesis of breast cancer. Further study emphasis is to understand the association of hPTTG1 with other genes in cancer progression. This novel modality might also consider for identification of targeted drugs, prognosis and follow up in breast cancer gene therapy.
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http://dx.doi.org/10.1016/j.lfs.2019.116873DOI Listing
December 2019

identification of novel lncRNAs with a potential role in diagnosis of gastric cancer.

J Biomol Struct Dyn 2020 Apr 8;38(7):1954-1962. Epub 2019 Jun 8.

Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.

Gastric cancer (GC) is the second leading cause of cancer-related deaths in the world. Due to the shortage of adequate symptoms in the early stages, it is diagnosed when the tumor has spread to distant organs. Early recognition of GC enhances the chance of successful treatment. Molecular mechanisms of GC are still poorly understood. LncRNAs are emerging as new players in cancer in both oncogene and tumor suppressor roles. High-throughput technologies such as RNA-Seq, have revealed thousands of lncRNAs which are dysregulated in GC. In this study, we retrieved lncRNAs obtained by High-throughput technologies from OncoLnc database. Consequently, retrieved lncRNAs were compared in literature-based databases including PubMed. As a result, two lists, including experimentally validated lncRNAs and predicted lncRNAs were provided. We found 43 predicted lncRNAs that had not been experimentally validated in GC, so far. Further Bioinformatics analyses were performed to obtain the expression profile of predicted lncRNAs in tumor and normal tissues. Also, the roles and targets of predicted lncRNAs in GC were identified by related databases. Finally, using the GEPIA database was reviewed the significant relationship of predicted lncRNAs with the survival of GC patients. By recognizing the lncRNAs involved in initiation and progression of GC, they may be considered as potential biomarkers in the GC early diagnosis or targeted treatment and lead to novel therapeutic strategies. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1624615DOI Listing
April 2020

Survivin, a Promising Gene for Targeted Cancer Treatment.

Asian Pac J Cancer Prev 2016 ;17(8):3711-9

Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran E-mail : [email protected] yahoo.co.uk,

Drawbacks of conventional cancer treatments, with lack of specificity and cytotoxicity using current approaches, underlies the necessity for development of a novel approach, gene-directed cancer therapy. This has provided novel technological opportunities in vitro and in vivo. This review focuses on a member of an apoptosis inhibitor family, survivin, as a valuable target. Not only the gene but also its promoter are applicable in this context. This article is based on a literature survey, with especial attention to RNA interference as well as tumor- specific promoter action. The search engine and databases utilized were Science direct, PubMed, MEDLINE and Google. In addition to cell-cycle modulation, apoptosis inhibition, interaction in cell-signaling pathways, cancer-selective expression, survivin also may be considered as specific target through its promoter as a novel treatment for cancer. Our purpose in writing this article was to create awareness in researchers, emphasizing relation of survivin gene expression to potential cancer treatment. The principal result and major conclusion of this manuscript are that survivin structure, biological functions and applications of RNA interference systems as well as tumor-specific promoter activity are of major interest for cancer gene therapy.
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January 2017

Application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract.

Epidemiol Health 2016 4;38:e2016005. Epub 2016 Feb 4.

Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Objectives: Cataract is a prevalent disease in the elderly, and negatively influences patients' quality of life. This study was conducted to study the application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract.

Methods: In this cross-sectional study, 300 patients with cataract were studied in Neyshabur, Iran from July to October 2014. The Iranian version of the WHOQOL-BREF questionnaire was used to measure their quality of life. Cronbach's alpha coefficient, Pearson's correlation coefficient, the paired t-test, the independent t-test, and a linear regression model were used to analyze the data in SPSS version 16.0 (SPSS Inc., Chicago, IL, USA).

Results: The mean age of the participants was 68.11±11.98 years, and most were female (53%). The overall observed Cronbach's alpha coefficient for the WHOQOL-BREF was 0.889, ranging from 0.714 to 0.810 in its four domains. The total mean score of the respondents on the WHOQOL-BREF was 13.19. The highest and lowest mean scores were observed in the social relationship domain (14.11) and the physical health domain (12.29), respectively. A backward multiple linear regression model found that duration of disease and marital status were associated with total WHOQOL scores, while age, duration of disease, marital status, and income level were associated with domains one through four, respectively (p<0.05).

Conclusions: The reliability analysis conducted in this study indicated that the WHOQOL-BREF scale exhibited an acceptable degree of internal consistency in the measurement of the quality of life of patients with cataract. It was also found that the patients with cataract who were surveyed reported a relatively moderate quality of life.
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http://dx.doi.org/10.4178/epih.e2016005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877517PMC
February 2017

Induction of pluripotency in human umbilical cord mesenchymal stem cells in feeder layer-free condition.

Tissue Cell 2015 Dec 24;47(6):575-82. Epub 2015 Apr 24.

Department of Biomedical Science, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Induced Pluripotent Stem Cells (iPSCs) has been produced by the reprogramming of several types of somatic cells through the expression of different sets of transcription factors. This study consists of a technique to obtain iPSCs from human umbilical cord mesenchymal stem cells (UC-MSCs) in a feeder layer-free process using a mini-circle vector containing defined reprogramming genes, Lin28, Nanog, Oct4 and Sox2. The human MSCs transfected with the minicircle vector were cultured in iPSCs medium. Human embryonic stem cell (ESC)-like colonies with tightly packed domelike structures appeared 7-10 days after the second transfection. In the earliest stages, the colonies were green fluorescence protein (GFP)-positive, while upon continuous culture and passage, genuine hiPSC clones expressing GFP were observed. The induced cells, based on the ectopic expression of the pluripotent markers, exhibited characteristics similar to the embryonic stem cells. These iPSCs demonstrated in vitro capabilities for differentiation into the three main embryonic germ layers by embryoid bodies formation. There was no evidence of transgenes integration into the genome of the iPSCs in this study. In conclusion, this method offers a means of producing iPSCs without viral delivery that could possibly overcome ethical concerns and immune rejection in the use of stem cells in medical applications.
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http://dx.doi.org/10.1016/j.tice.2015.04.005DOI Listing
December 2015

PAMAM dendrimer roles in gene delivery methods and stem cell research.

Cell Biol Int 2013 May 18;37(5):415-9. Epub 2013 Mar 18.

Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.

Nanotechnology has provided new technological opportunities, which could help in challenges confronting stem cell research. Polyamidoamine (PAMAM) dendrimers, a new class of macromolecular polymers with high molecular uniformity, narrow molecular distribution specific size and shape and highly functionalised terminal surface have been extensively explored for biomedical application. PAMAM dendrimers are also nanospherical, hyperbranched and monodispersive molecules exhibiting exclusive properties which make them potential carriers for drug and gene delivery.
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http://dx.doi.org/10.1002/cbin.10051DOI Listing
May 2013

Comparison of tamoxifen with edible seaweed (Eucheuma cottonii L.) extract in suppressing breast tumor.

Nutr Cancer 2013 ;65(2):255-62

Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

The tropical edible red seaweed (Eucheuma cottonii L.) is rich in nutrients and polyphenolic compounds that may suppress cancer through its antioxidant and antiproliferative properties. The study reports on rat mammary tumor suppression and tissue antioxidant status modulation by E. cottonii ethanol extract (ECE). The effect of orally administered ECE (100 mg/kg body-weight) was compared with that of tamoxifen (10 mg/kg body-weight). Rat was induced to develop mammary tumor with subcutaneous injection of LA-7 cells (6 × 10(6) cells/rat). The ECE was more effective than tamoxifen in suppressing tumor growth (27%), improving tissues (plasma, liver, and kidney) malondialdehyde concentrations, superoxide dismutase activity and erythrocyte glutathione concentrations (P < 0.05). Unlike tamoxifen, the ECE displayed little toxicity to the liver and kidneys. The ECE exhibited strong anticancer effect with enzyme modulating properties, suggesting its potential as a suppressing agent for mammary gland tumor.
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http://dx.doi.org/10.1080/01635581.2013.756528DOI Listing
December 2013
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