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Cancer Research Center, Shohada Tajrish Hospital
Shahid Beheshti University of Medical Sciences
Mohammad Reza Zinatizadeh, Bettina Schock, Ghanbar Mahmoodi Chalbatani, Peyman Kheirandish Zarandi, Seyed Amir Jalali, and Seyed Rouhollah Miri
Genes and Diseases, eISSN: 23523042, Published: 2020 Elsevier BV
Abstract The nuclear factor kappa B (NF-eB) family of transcription factors plays an essential role as stressors in the cellular environment, and controls the expression of important regulatory genes such as immunity, inflammation, death, and cell proliferation. NF-eB protein is located in the cytoplasm, and can be activated by various cellular stimuli. There are two pathways for NF-eB activation, as the canonical and non-canonical pathways, which require complex molecular interactions with adapter proteins and phosphorylation and ubiquitinase enzymes. Accordingly, this increases NF-eB translocation in the nucleus and regulates gene expression. In this study, the concepts that emerge in different cellular systems allow the design of NF-eB function in humans. This would not only allow the development for rare diseases associated with NF-eB, but would also be used as a source of useful information to eliminate widespread consequences such as cancer or inflammatory/immune diseases.
Hassan Dana, Ghanbar Mahmoodi Chalbatani, Elahe Gharagouzloo, Seyed Rouhollah Miri, Fereidoon Memari, Reza Rasoolzadeh, Mohammad Reza Zinatizadeh, Peyman Kheirandish Zarandi, and Vahid Marmari
Drug Design, Development and Therapy, eISSN: 11778881, Pages: 309-329, Published: 2020 Informa UK Limited
Introduction Colorectal cancer (CRC) is a type of cancer in humans that leads to high mortality and morbidity. CD166 and CD326 are immunoglobulins that are associated with cell migration. These molecules are included in tumorigenesis of CRC and serve a great marker of CRC stem cells. In the present study, we devised a novel chimeric protein including the V1-domain of the CD166 and two epitopes of CD326 to use in diagnostic or therapeutic applications. Methods In silico techniques were launched to characterize the properties and structure of the protein. We have predicted physicochemical properties, structures, stability, MHC class I binding properties and ligand-receptor interaction of this chimeric protein by means of computational bioinformatics tools and servers. The sequence of chimeric gene was optimized for expression in prokaryotic host using online tools and cloned into pET-28a plasmid. The recombinant pET28a was transformed into the E. coli BL21DE3. Expression of recombinant protein was examined by SDS-PAGE and Western blotting. Results The designed chimeric protein retained high stability and the same immunogenicity as of the original proteins. Bioinformatics data indicated that the epitopes of the synthetic chimeric protein might induce B-cell- and T-cell-mediated immune responses. Furthermore, a gene was synthesized using the codon bias of a prokaryotic expression system. This synthetic gene expressed a bacterial expression system. The recombinant protein with molecular weights of 27kDa was expressed and confirmed by anti-his Western blot analysis. Conclusion The designed recombinant protein may be useful as a CRC diagnostic tool and for developing a protective vaccine against CRC.
Iranian Journal of Pharmaceutical Research, ISSN: 17350328, eISSN: 17266890, Pages: 232-240, Published: 1 December 2019
Mohammad Reza Zinatizadeh, Seyed Ali Momeni, Peyman Kheirandish Zarandi, Ghanbar Mahmoodi Chalbatani, Hassan Dana, Hamid Reza Mirzaei, Mohammad Esmaeil Akbari, and Seyed Rouhollah Miri
Genes and Diseases, eISSN: 23523042, Pages: 378-384, Published: December 2019 Elsevier BV
Ras gene mutation has been observed in more than 30% of cancers, and 90% of pancreatic, lung and colon cancers. Ras proteins (K-Ras, H-Ras, N-Ras) act as molecular switches which are activated by binding to GTP. They play a role in the cascade of cell process control (proliferation and cell division). In the inactive state, transforming GTP to GDP leads to the activation of GTpase in Ras gene. However, the mutation in Ras leads to the loss of internal GTPase activity and permanent activation of the protein. The activated Ras can promote the cell death or stop cell growth, which are facilitated by Ras-association domain family. Various studies have been conducted to determine the importance of losing RASSF proteins in Ras-induced tumors. This paper examines the role of Ras and RASSF proteins. In general, RASSF proteins can be used as a suitable means for targeting a large group of Ras-induced tumors.
Mohammad Reza Zinatizadeh, Seyed Rouhollah Miri, Peyman Kheirandish Zarandi, Ghanbar Mahmoodi Chalbatani, Catarina Rapôso, Hamid Reza Mirzaei, Mohammad Esmaeil Akbari, and Habibollah Mahmoodzadeh
Genes and Diseases, eISSN: 23523042, Published: 2019 Elsevier BV
Abstract Hippo Tumor Suppressor Pathway is the main pathway for cell growth that regulates tissue enlargement and organ size by limiting cell growth. This pathway is activated in response to cell cycle arrest signals (cell polarity, transduction, and DNA damage) and limited by growth factors or mitogens associated with EGF and LPA. The major pathway consists of the central kinase of Ste20 MAPK (Saccharomyces cerevisiae), Hpo (Drosophila melanogaster) or MST kinases (mammalian) that activates the mammalian AGC kinase dmWts or LATS effector (MST and LATS). YAP in the nucleus work as a cofactor for a wide range of transcription factors involved in proliferation (TEA domain family, TEAD1-4), stem cells (Oct4 mononuclear factor and SMAD-related TGFβ effector), differentiation (RUNX1), and Cell cycle/apoptosis control (p53, p63, and p73 family members). This is due to the diverse roles of YAP and may limit tumor progression and establishment. TEAD also coordinates various signal transduction pathways such as Hippo, WNT, TGFβ and EGFR, and effects on lack of regulation of TEAD cancerous genes, such as KRAS, BRAF, LKB1, NF2 and MYC, which play essential roles in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. However, RAS signaling is a pivotal factor in the inactivation of Hippo, which controls EGFR-RAS-RAF-MEK-ERK-mediated interaction of Hippo signaling. Thus, the loss of the Hippo pathway may have significant consequences on the targets of RAS-RAF mutations in cancer.