scholarly journals In silico screening and analysis of nonsynonymous SNPs in human CYP1A2 to assess possible associations with pathogenicity and cancer susceptibility

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leila Navapour ◽  
Navid Mogharrab
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Susceptibility ◽  
Interaction Network ◽  
Significant Rise ◽  
Nucleotide Polymorphisms ◽  
Cancer Driver ◽  
Redox Partners ◽  
Dynamics Simulations ◽  
Intramolecular Hydrogen ◽  
Drug Efficiency

AbstractCytochrome P450 1A2 (CYP1A2) is one of the main hepatic CYPs involved in metabolism of carcinogens and clinically used drugs. Nonsynonymous single nucleotide polymorphisms (nsSNPs) of this enzyme could affect cancer susceptibility and drug efficiency. Hence, identification of human CYP1A2 pathogenic nsSNPs could be of great importance in personalized medicine and pharmacogenetics. Here, 176 nsSNPs of human CYP1A2 were evaluated using a variety of computational tools, of which 18 nsSNPs were found to be associated with pathogenicity. Further analysis suggested possible association of 9 nsSNPs (G73R, G73W, R108Q, R108W, E168K, E346K, R431W, F432S and R456H) with the risk of hepatocellular carcinoma. Molecular dynamics simulations revealed higher overall flexibility, decreased intramolecular hydrogen bonds and lower content of regular secondary structures for both cancer driver variants G73W and F432S when compared to the wild-type structure. In case of F432S, loss of the conserved hydrogen bond between Arg137 and heme propionate oxygen may affect heme stability and the observed significant rise in fluctuation of the CD loop could modify CYP1A2 interactions with its redox partners. Together, these findings propose CYP1A2 as a possible candidate for hepatocellular carcinoma and provide structural insights into how cancer driver nsSNPs could affect protein structure, heme stability and interaction network.

scholarly journals Ranking cancer drivers via betweenness-based outlier detection and random walks

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Cesim Erten ◽  
Aissa Houdjedj ◽  
Hilal Kazan
Keyword(s):  
Cancer Genomics ◽  
Interaction Network ◽  
Molecular Data ◽  
Alternative Methods ◽  
Patient Specific ◽  
Cancer Genes ◽  
Driver Genes ◽  
Cancer Driver ◽  
Protein Protein Interaction ◽  
Genomic Studies

Abstract Background Recent cancer genomic studies have generated detailed molecular data on a large number of cancer patients. A key remaining problem in cancer genomics is the identification of driver genes. Results We propose BetweenNet, a computational approach that integrates genomic data with a protein-protein interaction network to identify cancer driver genes. BetweenNet utilizes a measure based on betweenness centrality on patient specific networks to identify the so-called outlier genes that correspond to dysregulated genes for each patient. Setting up the relationship between the mutated genes and the outliers through a bipartite graph, it employs a random-walk process on the graph, which provides the final prioritization of the mutated genes. We compare BetweenNet against state-of-the art cancer gene prioritization methods on lung, breast, and pan-cancer datasets. Conclusions Our evaluations show that BetweenNet is better at recovering known cancer genes based on multiple reference databases. Additionally, we show that the GO terms and the reference pathways enriched in BetweenNet ranked genes and those that are enriched in known cancer genes overlap significantly when compared to the overlaps achieved by the rankings of the alternative methods.

scholarly journals Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Acid Metabolism ◽  
Family Members ◽  
Interaction Network ◽  
Genetic Alterations ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Canonical Pathways ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

scholarly journals Car–Parrinello and path integral molecular dynamics study of the intramolecular hydrogen bonds in the crystals of benzoylacetone and dideuterobenzoylacetone

2014 ◽  
Vol 16 (42) ◽  
pp. 23026-23037 ◽  
Author(s):  
Piotr Durlak ◽  
Zdzisław Latajka
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Ab Initio ◽  
Path Integral ◽  
Molecular Crystal ◽  
Short Hydrogen Bond ◽  
Deuterated Analogue ◽  
Dynamics Simulations ◽  
Intramolecular Hydrogen

The dynamics of the intramolecular short hydrogen bond in the molecular crystal of benzoylacetone and its deuterated analogue are investigated using ab initio molecular dynamics simulations.

scholarly journals Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population

Oncotarget ◽  
2017 ◽  
Vol 8 (45) ◽  
pp. 80039-80049 ◽  
Author(s):  
Xiaonian Zhu ◽  
Wei Liu ◽  
Xiaoqiang Qiu ◽  
Zhigang Wang ◽  
Chao Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
Poor Prognosis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals The Effects of the Solvents on the Macrocyclic Structures: From Rigid Pillararene to Flexible Crown Ether

2021 ◽  
Author(s):  
Shuangshuang Wang ◽  
Yanzhen Yin ◽  
Jian Gao ◽  
Xingtang Liang ◽  
Haixin Shi
Keyword(s):  
Hydrogen Bonds ◽  
Structural Design ◽  
Structural Features ◽  
Intermolecular Hydrogen Bonds ◽  
Intramolecular Hydrogen Bonds ◽  
Effect Of Solvents ◽  
Dynamics Simulations ◽  
Intramolecular Hydrogen ◽  
Macrocyclic Molecules ◽  
Polarity Of Solvents

The differences in the macrocyclic structures lead to different flexibilities, and yet the effect of solvents on the conformations is not clear so far. In this work, the conformations of four representational macrocyclic molecules (pillar[5]arene, p-tert-butyl calix[6]arene, benzylic amide macrocycle and dibenzo-18-crown-6) in three solvents with distinct polarity have been studied by all-atom molecular dynamics simulations. The structural features of the macrocycles in the solvents indicate that the conformations are related to the polarity of the solvents and the formation of hydrogen bonds. For the pillar[5]arene, the benzylic amide macrocycle and the dibenzo-18-crown-6, that cannot form intramolecular hydrogen bonds, the polarity of solvents is the major contributing factor in the conformations. The formation of intramolecular hydrogen bonds, in contrast, determinates the conformations of the calix[6]arene. Furthermore, the slight fluctuations of the structures will result in tremendous change of the intramolecular hydrogen bonds of the macrocycles and the intermolecular hydrogen bonds between the macrocycles and the solvents. The current theoretical studies that serve as a basis for the macrocyclic chemistry are valuable for the efficient structural design of the macrocyclic molecules.

scholarly journals The development of rs7107217 genotyping method and initial study of the association of this gene with the breast cancer risk in Vietnamese women

2019 ◽  
Vol 2 (5) ◽  
pp. 40-49
Author(s):  
Thanh Thi Ngoc Nguyen ◽  
Giau Thi Ngoc Mai ◽  
Hue Thi Nguyen
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Regulation Of Gene Expression ◽  
High Sensitivity ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Cancer Susceptibility Genes ◽  
And Control

Breast cancer is the most common cancer for women around the world. The presence of single nucleotide polymorphisms (SNP) on or near the coding region of breast cancer susceptibility genes can affect the regulation of gene expression, which may increase or decrease the risk of breast cancer. BARX2 was showed to stimulate the expression of ERS1, which involved in the development of breast cancer. SNP rs7107217 on 152kb downstream of the BARX2 could affect the level of protein BARX2 and had been proved to associate with the breast cancer risk in populations similar to Vietnamese, including Chinese and Korean. In this study, rs7107217 was genotyped and initially detemined the association with the breast cancer risk in Vietnamese. Real-time PCR HRM was optimized and used to genotype rs7107217 in 117 breast cancer cases and 105 healthy controls. Thereafter, the correlation of this SNP with the risk of breast cancer was initially determined by analyzing the differences in allelic and genotypic frequencies between cases and control groups. The results showed the optimal rs7107217 genotyping condition was successfully developed with the high sensitivity, specificity, and consistency. SNP rs7107217 had high polymorphism with the frequency of minor allele C of 29.9% and 35.3% in case and control, respectively. SNP rs7107217 had been found no association with the breast cancer risk (C vs A: P = 0.23, OR (95% CI) = 0.79 (0.53 – 1.17)). However with the low reliability of the analysis (11.71%) and the high potential related to the formation of breast cancer, the association between rs7107217 and breast cancer risk in Vietnamese population should be further conducted on a larger sample size to get higher accuracy.

Identification and validation of a hub gene prognostic index for hepatocellular carcinoma

2021 ◽  
Author(s):  
Q Shi ◽  
Z Meng ◽  
XX Tian ◽  
YF Wang ◽  
WH Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Prognostic Index ◽  
Interaction Network ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
Cox Regression Analysis ◽  
Protein Protein Interaction ◽  
Normal Tissues ◽  
Significant Independent Prognostic Factor

Aims: We aim to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) and identify key genes as biomarkers for the prognosis of HCC. Materials & methods: Differentially expressed genes between HCC tissues and normal tissues were identified via the Gene Expression Omnibus tool. The top ten hub genes screened by the degree of the protein nodes in the protein–protein interaction network also showed significant associations with overall survival in HCC patients. Results: A prognostic model containing a five-gene signature was constructed to predict the prognosis of HCC via multivariate Cox regression analysis. Conclusion: This study identified a novel five-gene signature ( CDK1, CCNB1, CCNB2, BUB1 and KIF11) as a significant independent prognostic factor.

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