scholarly journals In silico analysis and cluster validation of potential breast cancer nsSNPs of serological tumor marker CA27.29

2021 ◽  
Author(s):  
Jyoti Lakhani ◽  
Dharmesh Harwani
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Critical Role ◽  
In Silico Analysis ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
Synonymous Snps ◽  
Functional Roles ◽  
Serological Tumor ◽  
Validation Of Results

ABSTRACTBackground & ObjectivesCA27.29 is a breast cancer-associated glycoprotein. Many genetic variations caused by non-synonymous nucleotide polymorphisms (nsSNPs) are known to affect the functionality of the CA27.29 protein.MethodsIn the present manuscript, an in silico analysis of the genetic variations in CA27.29 was done to observe functional nsSNPs that possibly alter its stability. Among 2205 SNPs identified from the publically available SNP database (dbSNP), 213 (9.66%) synonymous SNPs, 24 (1.09%) non-synonymous SNPs, and 1351 (61.27%) noncoding intronic SNPs were observed. The function predictability tools SIFT, Provean and Polyphen2 were used to uncover variations in the analyzed nsSNPs and their functionality.ResultsA total of 16, 20 and 10 non-synonymous SNPs (nsSNPs) were predicted to be damaging or deleterious by SIFT, Polyphen, and Provean tools respectively. Intriguingly, 9 nsSNPs were predicted to be damaging by all the three tools used while 4 nsSNPs were predicted to be damaging by SIFT and Polyphen tools. The substitutions C/G->T and G->A/T were observed to be dominant in the analyzed nsSNPs that probably have damaging role to CA27.29 glycoprotein. Moreover, the validation of results using ClinVar tool revealed that all the analyzed possibly, probably and highly damaging nsSNPs are yet to be reported and studied. Besides this, we found Global minor allele frequency (Global MAF) for only 11 nsSNPs, the values of which were observed to be <0.1% that further confirmed the novelty of the analyzed variants.Interpretation & ConclusionsAmong the analyzed nsSNPs, 3 nsSNPs rs145691584, rs148332231 and rs191544901 were found to be located in 3’UTR region of CA27.29 gene that were assumed to have the possible functional roles in altering the protein stability. The present study is useful to gain useful insights into the genetic variations in nsSNPs that may playing a critical role in determining the susceptibility to breast cancer.

scholarly journals BRCA1 novel variation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1461
Author(s):  
Mohamed Elmogtba Mouaweia Mohamed Aabdein ◽  
Alsmawal Awad Mohammed Elimam ◽  
Hisham N. Altayb ◽  
Mohamed El-Fatih Mohy Eldeen ◽  
Mosab Mohamed Gasemelseed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Disease Onset ◽  
In Silico Analysis ◽  
Diagnostic Value ◽  
Nucleotide Polymorphisms ◽  
Protein Activity ◽  
Exon 11 ◽  
Exon 20 ◽  
Novel Snp

Background: Breast cancer (BC) remains one of the leading causes of death in women worldwide. The BRCA1 deleterious mutation has a significant role in developing BC, and the risk has been estimated to be 46–87%. Many studies emphasize the need for mining BRCA1 gene mutations that might have a role in BC pathogenesis and could affect early disease onset. This study was conducted to screen for possible pathogenic single nucleotide polymorphisms (SNPs) in BRCA1, targeting three regions: two in exon 11 and the third in exon 20. Methods: 45 blood samples were collected from patients diagnosed with BC. DNA was extracted and selected regions were amplified by PCR using three sets of primers - two within exon 11 and one within exon 20 of BRCA1. Subsets of 10 samples were selected for each primer set (30 PCR products) and sequenced. Sequences were analyzed using various bioinformatics tools. Results: Two missense variations were found, Q356R (rs1799950) in one patient (27 years old) and a novel SNP, V1736D, in three premenopausal patients (≤45 years), which were located within exons 11 and 20, respectively. Both detected variants were heterozygous, a status found in all patients detected with such monoallelic variation. Both missense variants underwent in silico analysis. The well-known variation, rs1799950, was predicted to alter the protein activity, conferred by a mutant residue (R-Arg), owing to the position with a bigger size and positive charge. The novel SNP, V1736D, was predicted to play a role in the pathogenesis of BC. Conclusion: Both variants require further investigation, firstly to assess their contribution to BC and secondly to determine their potential diagnostic value when assessed in a larger population.

scholarly journals The expression of miR-513c and miR-3163 was downregulated in tumor tissues compared with normal adjacent tissue of patients with breast cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Soheila Delgir ◽  
Khandan Ilkhani ◽  
Asma Safi ◽  
Yazdan Rahmati ◽  
Vahid Montazari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Silico ◽  
Target Genes ◽  
Critical Role ◽  
In Silico Analysis ◽  
Glutamine Metabolism ◽  
Biological Processes ◽  
Tumor Tissues ◽  
In Silico Studies ◽  
Silico Analysis

Abstract Background Breast cancer (BC) is the most invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered critical nutrition that many cancer cells, particularly BC cells, are dependent on it for growth and proliferation. Therefore, targeting glutamine metabolism, especially enzymes that are related to this pathway, can be beneficial to design anti-cancer agents. Recent evidence has shown that microRNAs (miRNAs), with a short length and single-strand properties, play a prominent role in regulating the genes related to glutamine metabolism, which may control the development of cancer. Methods In silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism. The expression level of these two miRNAs was evaluated in eighty BC tissues and normal adjacent tissues. Furthermore, GSE38167, GSE38867, GSE42128, GSE45666, and GSE53179 were employed from gene expression omnibus (GEO). The Limma package was utilized to identify differentially expressed miRNAs (DEMs) of mentioned datasets to evaluate miR-513c and miR-3163 expression. Further, in silico analysis was utilized to predict the potential biological processes and molecular pathways of miR-513c and miR-3163, based on their target genes. Results In silico studies revealed top categories of biological processes and cellular pathways that might play a critical role in metabolism reprogramming and cancer development and were target genes for miR-513c and miR-3163. The current study showed that miR-513c (p value = 0.02062 and FC =  − 2.3801) and miR-3163 (p value = 0.02034 and FC =  − 2.3792) were downregulated in tumor tissues compared to normal adjacent tissues. The analysis of GEO microarray datasets showed that miR-513c was downregulated in GSE38167, GSE38867, GSE42128, GSE45666 and GSE53179, whereas there was a significant downregulation of miR-3163 in only two studies, including GSE38867 and GSE42128 that they were in accordance with our experimental results. Furthermore, the subgroup analysis did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history of cancer, and abortion history. Conclusion MiR-513c and miR-3163 were downregulated in BC tissues, which might serve as tumor suppressors. They are suggested as potential therapeutic targets for patients with BC.

In-silico analysis of non- synonymous SNPs of human LDLR gene and their impact on familial hypercholesterolemia

Gene Reports ◽  
2021 ◽  
pp. 101127
Author(s):  
Pratik Ghosh ◽  
Samarpita Ghosh ◽  
Bhaskar Behera ◽  
Jiban Kumar Behera ◽  
Manojit Bhattacharya ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
In Silico ◽  
In Silico Analysis ◽  
Ldlr Gene ◽  
Synonymous Snps ◽  
Silico Analysis

scholarly journals Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aner Mesic ◽  
Marija Rogar ◽  
Petra Hudler ◽  
Nurija Bilalovic ◽  
Izet Eminovic ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
In Silico ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mitotic Kinases ◽  
Genes Encoding ◽  
Silico Analysis ◽  
Control Study

Abstract Background Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). Methods Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. Results The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. Conclusions Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings.

scholarly journals The Expression of miR-513c and miR-3163 was Downregulated in Tumor Tissues Compared with Margin Tissues of Patients With Breast Cancer

2020 ◽  
Author(s):  
Soheila Delgir ◽  
Khandan Ilkhani ◽  
Asma Safi ◽  
Farhad Seif ◽  
Milad Bastami ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
In Silico ◽  
In Silico Analysis ◽  
Glutamine Metabolism ◽  
Expression Level ◽  
P Value ◽  
Biological Processes ◽  
Tumor Tissues ◽  
Silico Analysis

Abstract Background Breast cancer (BC) is the most common invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered a critical nutrition for tumor cell growth and therefore, targeting glutamine metabolism, especially Glutaminase, which catalyzed the conversion of glutamine to glutamate can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with short length and single strand properties play a significant role in regulating the genes related to glutamine metabolism and may control the development of cancer.Methods Since, in-silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism, the expression level of these two miRNAs was evaluated in eighty BC tissues and margin tissues. The data were analyzed to evaluate the correlation between expression level of these miRNAs and patient’s characteristics such as abortion history, family history, and age. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on its gene targets.Results In-silico studies revealed the top categories of biological processes and pathways that play a critical role in cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (P-value = 0.02062 and fold change= -2.3801) and miR-3163 (P-value = 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup studies did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion.Conclusion Based on our data, miR-513c and miR-3163 may be offered as a potential diagnosis and therapeutic targets for patients with BC.

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