ABSTRACT
The CD147 / Cyp A interaction is a critical pathway in cancer types and an essential factor in entering the COVID-19 virus into the host cell. Melittin acts as an inhibitory peptide in cancer types by blocking the CD147/ Cyp A interaction. The clinical application of Melittin is limited due to weak penetration into cancer cells. TAT is an arginine-rich peptide with high penetration ability into cells widely used in drug delivery systems. This study aimed to design a hybrid peptide derived from Melittin and TAT to inhibit CD147 /Cyp A interaction. An amino acid region with high anti-cancer activity in Melittin was selected based on the physicochemical properties. Based on the results, a truncated Melittin peptide with 15 amino acids by the GGGS linker was fused to a TAT peptide (nine amino acids) to increase the penetration rate into the cell. A new hybrid peptide analog(TM) was selected by replacing the glycine with serine based on random point mutation. Docking results indicated that the TM peptide acts as an inhibitory peptide with high binding energy when interacting with CD147 and the CypA proteins. RMSD and RMSF results confirmed the high stability of the TM peptide in interaction with CD147. Also, the coarse-grained simulation showed the penetration potential of TM peptide into the DOPS-DOPC model membrane. Our findings indicated that the designed multifunctional peptide could be an attractive therapeutic candidate to halter tumor types and COVID-19 infection.
ABSTRACT
Breast cancer is the most common malignancy among females worldwide. Recent studies have shown extra-ribosomal roles of the moonlight ribosomal proteins in the development of human cancers. Accurate quantification of the gene expression level is based on the selection of the reference genes whose expression is independent of cancer properties and patient's characteristics. The aim of this study was the evaluation of the expression level of a previously proposed ribosomal protein as moonlight, L13a (RPL13A), in breast cancer samples and their adjacent tissues. Its association with genes of known roles in developing cancers was also investigated. Traditionally used housekeeping genes were selected and their expression was analyzed in 80 surgically excised breast tissue specimens (40 tumors and 40 tumor-adjacent tissues) by applying three software tools including GeNorm, NormFinder, and BestKeeper to select the most stable reference genes. Then, mRNA expression levels of RPL13A and p53 were evaluated. Additionally, protein expression levels of RPL13A were measured. It was demonstrated that PUM1 and ACTB are the most reliable reference genes and RPL13A is the least stable gene. There was a positive correlation between RPL13A and p53 mRNA expression levels in all the tumor samples. Moreover, significant downregulation of RPL13A expression levels was revealed in HER2+ tumor samples compared to HER2- ones. There was also a marked decrease in p53 mRNA expression levels in HER2+ tumor subtypes. Our results suggest that there is a probable relationship between RPL13A decreased expression with p53 and HER2/neu expression in the breast cancer.
Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Ribosomal Proteins , Breast Neoplasms/genetics , Down-Regulation , Female , Humans , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
The CRISPR/Cas9 system is a precisely targeted bacterial defense system, used to control invading viruses. This technology has many potential applications including genetic changes in somatic and germ cells and the creation of knockout animals. Compared to other genome editing techniques such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENS), the CRISPR/Cas9 system is much easier and more efficient. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. The CRISPR/Cas9 system also potentially has the ability to prevent and treat human diseases. The present article addresses some key points related to the use of the CRISPR/Cas9 system as a powerful tool in cardiovascular research and as a new strategy for the treatment of cardiovascular disease (CVD).
Subject(s)
CRISPR-Associated Protein 9/genetics , CRISPR-Cas Systems , Cardiovascular Diseases/therapy , Clustered Regularly Interspaced Short Palindromic Repeats , Gene Editing/methods , Genetic Therapy/methods , Stem Cell Transplantation/methods , Animals , CRISPR-Associated Protein 9/metabolism , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/genetics , Cardiovascular Diseases/physiopathology , Gene Expression Regulation , Genetic Therapy/adverse effects , Humans , Stem Cell Transplantation/adverse effectsABSTRACT
"Moonlighting protein" is a term used to define a single protein with multiple functions and different activities that are not derived from gene fusions, multiple RNA splicing, or the proteolytic activity of promiscuous enzymes. Different proteinous constituents of ribosomes have been shown to have important moonlighting extra-ribosomal functions. In this review, we introduce the impact of key moonlight ribosomal proteins and dependent signal transduction in the initiation and progression of various cancers. As a future perspective, the potential role of these moonlight ribosomal proteins in the diagnosis, prognosis, and development of novel strategies to improve the efficacy of therapies for human cancers has been suggested.
Subject(s)
Carcinogenesis/genetics , Neoplasms/genetics , Ribosomal Proteins/genetics , Ribosomes/genetics , Humans , Neoplasms/pathology , Protein Conformation , RNA, Ribosomal/genetics , Signal Transduction/geneticsABSTRACT
The rate of human health care-associated infections caused by Acinetobacter baumannii has increased significantly in recent years for its remarkable resistance to desiccation and most antibiotics. Phospholipases, capable of destroying a phospholipid substrate, are heterologous group of enzymes which are believed to be the bacterial virulence determinants. There is a need for in silico studies to identify potential vaccine candidates. A. baumannii phospholipase D (PLD) role has been proved in increasing organism's resistance to human serum, destruction of host epithelial cell and pathogenesis in murine model. In this in silico study high potentials of A. baumannii PLD in elicitation of humoral and cellular immunities were elucidated. Thermal stability, long half-life, non-similarity to human and gut flora proteome and non-allergenicity were in a list of A. baumannii PLD positive properties. Potential epitopic sequences were also identified that could be used as peptide vaccines against A. baumannii and various other human bacterial pathogens.
