Elizabeth Cagle, Brent Lake, Anasua Banerjee, Jazmine Cuffee, Narendra Banerjee, Darla Gilmartin, Makaiyah Liverman, Shennel Brown, Erik Armstrong, Santanu Bhattacharya, Somiranjan Ghosh, Tanmoy Mandal, Hirendra Banerjee
Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cells of epithelial origin that promotes metastasis, drug resistance and cancer stem cell formation. Since the information regarding differential gene expression in TNBC cells and cell signaling events leading to EMT is limited, this investigation was done by comparing transcriptomic data generated by RNA isolation and sequencing of a EMT model TNBC cell line in comparison to regular TNBC cells. RNA sequencing and Ingenuity Pathway Software Analysis (IPA) of the transcriptomic data revealed several upregulated and downregulated gene expressions along with novel core canonical pathways including Sirtuin signaling, Oxidative Phosphorylation and Mitochondrial dysfunction events involved in EMT changes of the TNBC cells.
三阴性乳腺癌(TNBC)是一种死亡率和发病率非常高的恶性癌症。上皮向间充质转化(Epithelial to Mesenchymal Transition, EMT)是上皮来源的癌细胞中最常见的病理生理变化，可促进转移、耐药和癌症干细胞的形成。由于有关TNBC细胞中差异基因表达和导致EMT的细胞信号事件的信息有限，因此本研究通过将EMT模型TNBC细胞系的RNA分离和测序产生的转录组学数据与常规TNBC细胞进行比较来完成。RNA测序和转录组学数据的独创性途径软件分析(IPA)揭示了TNBC细胞EMT变化中涉及的一些上调和下调的基因表达以及新的核心规范途径，包括Sirtuin信号传导、氧化磷酸化和线粒体功能障碍事件。
{"title":"Analysis of Differential Gene Expression and Core Canonical Pathways Involved in the Epithelial to Mesenchymal Transition of Triple Negative Breast Cancer Cells by Ingenuity Pathway Analysis.","authors":"Elizabeth Cagle, Brent Lake, Anasua Banerjee, Jazmine Cuffee, Narendra Banerjee, Darla Gilmartin, Makaiyah Liverman, Shennel Brown, Erik Armstrong, Santanu Bhattacharya, Somiranjan Ghosh, Tanmoy Mandal, Hirendra Banerjee","doi":"10.4236/cmb.2023.132002","DOIUrl":"https://doi.org/10.4236/cmb.2023.132002","url":null,"abstract":"<p><p>Triple Negative Breast Cancer (TNBC) is a malignant form of cancer with very high mortality and morbidity. Epithelial to Mesenchymal Transition (EMT) is the most common pathophysiological change observed in cancer cells of epithelial origin that promotes metastasis, drug resistance and cancer stem cell formation. Since the information regarding differential gene expression in TNBC cells and cell signaling events leading to EMT is limited, this investigation was done by comparing transcriptomic data generated by RNA isolation and sequencing of a EMT model TNBC cell line in comparison to regular TNBC cells. RNA sequencing and Ingenuity Pathway Software Analysis (IPA) of the transcriptomic data revealed several upregulated and downregulated gene expressions along with novel core canonical pathways including Sirtuin signaling, Oxidative Phosphorylation and Mitochondrial dysfunction events involved in EMT changes of the TNBC cells.</p>","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Norma Flores-Holguín, Juan Frau, Daniel Glossman-Mitnik
{"title":"Computational Chemistry and Molecular Modeling Techniques for the Study of Micropeptin EI-964: Insights into Its Chemical Reactivity and Potential Pharmaceutical Properties","authors":"Norma Flores-Holguín, Juan Frau, Daniel Glossman-Mitnik","doi":"10.4236/cmb.2023.133003","DOIUrl":"https://doi.org/10.4236/cmb.2023.133003","url":null,"abstract":"","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135401012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nabaa Kamal Alshafei, Intisar Hassan Saeed, Mona Abdelrahman Mohamed Khaier
Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.
{"title":"Type-2 Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor toward Predicting Possible Association","authors":"Nabaa Kamal Alshafei, Intisar Hassan Saeed, Mona Abdelrahman Mohamed Khaier","doi":"10.4236/cmb.2023.133004","DOIUrl":"https://doi.org/10.4236/cmb.2023.133004","url":null,"abstract":"Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135698941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Personalized Digital Code from Unique Genome Fingerprinting Pattern for Use in Identification and Application on Blockchain","authors":"Isaac Kise Lee","doi":"10.4236/cmb.2023.131001","DOIUrl":"https://doi.org/10.4236/cmb.2023.131001","url":null,"abstract":"","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70445422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Krauss, Chelsey Aurelus, Kayla Johnston, J. Hedley, Satyendra N. Banerjee, Sarah Wisniewski, Quentin Reaves, Khadimou Dia, S. Brown, Victoria Bartlet, Sheritta Gavin, Jazmine Cuffee, Narendra Banerjee, Kuldeep Rawat, S. Mandal, Z. Abedin, Somiranjan Ghosh, H. Banerjee
Rhenium compounds have shown anti-cancer properties against many different types of cancer cell lines; however, the cellular signaling mechanisms involved in the cytotoxic properties of rhenium-based compounds were never deciphered or reported. In this manuscript, we report the results of an investigation done by RNA sequencing of rhenium treated A549 lung cancer cell lines along with an untreated vehicular control, analyzed by the Ingenuity Pathway Analysis (IPA) software system to decipher the core canonical pathways involved in rhenium induced cancer cell death. A549 EMT lung cancer cell lines were treated with rhenium ligand (Tricarbonylperrhenato(bathocuproine)rhenium(I), PR7) for seven days along with vehicular control. RNA was isolated from the treated and control cells and sequenced by a commercial company (PrimBio Corporation). The RNA sequencing data was analyzed by the INGNUITY software system and the core canonical pathways involved with differential gene expression were identified. Our report is showing that there are several cellular pathways involved in inducing cell death by rhenium-based compound PR7.
{"title":"A Study of Differential Gene Expression and Core Canonical Pathways Involved in Rhenium Ligand Treated Epithelial Mesenchymal Transition (EMT) Induced A549 Lung Cancer Cell Lines by INGENUITY Software System","authors":"C. Krauss, Chelsey Aurelus, Kayla Johnston, J. Hedley, Satyendra N. Banerjee, Sarah Wisniewski, Quentin Reaves, Khadimou Dia, S. Brown, Victoria Bartlet, Sheritta Gavin, Jazmine Cuffee, Narendra Banerjee, Kuldeep Rawat, S. Mandal, Z. Abedin, Somiranjan Ghosh, H. Banerjee","doi":"10.4236/cmb.2022.121002","DOIUrl":"https://doi.org/10.4236/cmb.2022.121002","url":null,"abstract":"Rhenium compounds have shown anti-cancer properties against many different types of cancer cell lines; however, the cellular signaling mechanisms involved in the cytotoxic properties of rhenium-based compounds were never deciphered or reported. In this manuscript, we report the results of an investigation done by RNA sequencing of rhenium treated A549 lung cancer cell lines along with an untreated vehicular control, analyzed by the Ingenuity Pathway Analysis (IPA) software system to decipher the core canonical pathways involved in rhenium induced cancer cell death. A549 EMT lung cancer cell lines were treated with rhenium ligand (Tricarbonylperrhenato(bathocuproine)rhenium(I), PR7) for seven days along with vehicular control. RNA was isolated from the treated and control cells and sequenced by a commercial company (PrimBio Corporation). The RNA sequencing data was analyzed by the INGNUITY software system and the core canonical pathways involved with differential gene expression were identified. Our report is showing that there are several cellular pathways involved in inducing cell death by rhenium-based compound PR7.","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43774037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>H</i><sub>2</sub> and <i>H</i><sub>∞</sub>-Feedback Control Design for Nonlinear Gene Networks via Successive Galerkin’s Approximation","authors":"Alexander W. Bae","doi":"10.4236/cmb.2022.122006","DOIUrl":"https://doi.org/10.4236/cmb.2022.122006","url":null,"abstract":"","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70445149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme that plays an important role in purinecarbon metabolism and thymidine biosynthesis. It has attracted broad interest as a novel therapeutic target for cancer. However, a major problem of current MTHFD2 inhibitors is their lack of selectivity and reactivity with its closest isoform, MTHFD1. Recently, the first selective MTHFD2 inhibitor, DS44960156, has been reported and it exhibits a more than 18-fold selectivity for MTHFD2 over MTHFD1. However, mechanism of DS44960156 selective binding to MTHFD2 over MTHFD1 is unknown. In this study, molecular docking, molecular dynamics (MD) simulations, molecular mechanics generalized born/surface area (MM_GBSA) binding free energy calculations, and analysis of the decomposition of binding free energies were used to investigate the selective binding mechanism of DS44960156 to the folate-binding site of MTHFD2 over MTHFD1. The results revealed that contributions from residues Gln100/Gln132, Val55/Asn87, and Gly237/Gly310 in the binding pocket of MTHFD1/MTHFD2 are the key factors responsible for the binding selectivity. These findings explain the selectivity of DS44960156 to MTHFD2 over MTHFD1, and may provide guidance for the future study and design of novel MTHFD2 inhibitors.
亚甲基四氢叶酸脱氢酶2 (MTHFD2)是一种线粒体酶，在嘌呤碳代谢和胸腺嘧啶生物合成中起重要作用。它作为一种新的癌症治疗靶点引起了广泛的兴趣。然而，目前MTHFD2抑制剂的一个主要问题是它们缺乏选择性和与其最接近的异构体MTHFD1的反应性。最近，第一个选择性MTHFD2抑制剂DS44960156被报道，它对MTHFD2的选择性比MTHFD1高18倍以上。然而，DS44960156选择性结合MTHFD2而非MTHFD1的机制尚不清楚。本研究采用分子对接、分子动力学(MD)模拟、分子力学广义born/surface area (MM_GBSA)结合自由能计算、结合自由能分解分析等方法，研究DS44960156在MTHFD1上选择性结合MTHFD2叶酸结合位点的机制。结果表明，MTHFD1/MTHFD2结合口袋中的残基Gln100/Gln132、Val55/Asn87和Gly237/Gly310是影响其结合选择性的关键因素。这些发现解释了DS44960156对MTHFD2优于MTHFD1的选择性，可能为未来新型MTHFD2抑制剂的研究和设计提供指导。
{"title":"Molecular Modeling and Molecular Dynamics Simulation Studies on the Selective Binding Mechanism of MTHFD2 Inhibitors","authors":"Mengyang Qu","doi":"10.4236/cmb.2022.121001","DOIUrl":"https://doi.org/10.4236/cmb.2022.121001","url":null,"abstract":"Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme that plays an important role in purinecarbon metabolism and thymidine biosynthesis. It has attracted broad interest as a novel therapeutic target for cancer. However, a major problem of current MTHFD2 inhibitors is their lack of selectivity and reactivity with its closest isoform, MTHFD1. Recently, the first selective MTHFD2 inhibitor, DS44960156, has been reported and it exhibits a more than 18-fold selectivity for MTHFD2 over MTHFD1. However, mechanism of DS44960156 selective binding to MTHFD2 over MTHFD1 is unknown. In this study, molecular docking, molecular dynamics (MD) simulations, molecular mechanics generalized born/surface area (MM_GBSA) binding free energy calculations, and analysis of the decomposition of binding free energies were used to investigate the selective binding mechanism of DS44960156 to the folate-binding site of MTHFD2 over MTHFD1. The results revealed that contributions from residues Gln100/Gln132, Val55/Asn87, and Gly237/Gly310 in the binding pocket of MTHFD1/MTHFD2 are the key factors responsible for the binding selectivity. These findings explain the selectivity of DS44960156 to MTHFD2 over MTHFD1, and may provide guidance for the future study and design of novel MTHFD2 inhibitors.","PeriodicalId":70839,"journal":{"name":"计算分子生物学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70444678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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