Department of Biochemistry

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    Molecular Docking Appraisal of Pleurotus ostreatus Phytochemicals as Potential Inhibitors of PI3K/Akt Pathway for Breast Cancer Treatment
    (Bioinformatics and Biology Insights Volume 19:, 2025) Effiong, Magdalene Eno; Bella-Omunagbe, Mercy; Afolabi, Israel Sunmola; Chinedu, Shalom Nwodo
    InTRoDuCTIon: Breast cancer (BC) is a heterogeneous disease involving a network of numerous extracellular signal transduction path ways. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mechanistic target of rapamycin (mTOR) pathway is crucial for understanding the BC development. Phosphoinositide 3-kinase, phosphatase and tensin homolog (PTEN), mTOR, Akt, 3-phosphoinositide dependent kinase 1 (PDK1), FoxO1, glycogen synthase kinase 3 (GSK-3), mouse double minute 2 (MDM2), H-Ras, and proapoptotic B-cell lymphoma 2 (BCL-2) family protein (BAD) proteins are key drivers of this pathway and potential therapeutic targets. Pleurotus ostreatus is an edible mushroom that is rich in flavonoids and phenols that can serve as potential inhibitors of proteins in the PI3K/Akt/mTOR pathway. AIM: This study evaluated the anticancer properties of P ostreatus through a structure-based virtual screening of 22 biologically active com pounds present in the mushroom. MeThoD: Model optimization was carried out on PI3K, PTEN, mTOR, Akt, PDK1, FoxO1, GSK-3, MDM2, H-Ras, and BAD proteins in the PI3K/Akt/mTOR pathway and molecular docking of compounds/control inhibitors in the binding pocket were simulated AutoDock Vina in PyRx. The drug likeness, pharmacokinetic, and pharmacodynamic features of prospective docking leads were all anticipated. ReSulT: Several potent inhibitors of the selected key driver proteins in PI3K/Akt/mTOR pathway were identified from P ostreatus. Ellagic acid with binding affinities of −8.0, −8.0, −8.1, −8.2, −6.2, and −7.1 kcal/mol on PI3K, Akt, PDK1, GSK-3, MDM2, and BAD, respectively, had better binding affinity compared with their reference drugs. Likewise, apigenin (−7.8 kcal/mol), chrysin (−7.8 kcal/mol), quercetin (−6.4 kcal/ mol), and chlorogenic acid (−6.2 kcal/mol) had better binding affinities to PTEN, mTOR, FoxO1, and H-Ras proteins, respectively. ConCluSIon: Ellagic acid, apigenin, luteolin, quercetin, chlorogenic acid, chrysin, and naringenin phytochemicals are seen as the better lead molecules due to their ability to strongly bind to the proteins under study in this pathway. Analogs of these compounds can also be designed as potential drugs.
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    Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients
    (Technology in Cancer Research & Treatment Volume 24, 2025) Onyia, Abimbola F.; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunmi, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B; Nkom, Ebenezer S.; De Campos, Opeyemi C.; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.
    Background: Breast cancer remains a leading cause of mortality among Nigerian women, with triple-negative breast cancer (TNBC) being particularly prevalent. Variations in BRCA1 and BRCA2 genes remain key risk factors for this disease. However, there are gaps in the frequency and spectrum of these variants in Nigerian populations, as well as a dearth in the local capacity to characterize these variations. Objective: This study aimed at identifying and characterizing the germline variations in BRCA1/2 in Nigerian breast cancer patients and healthy age-matched controls to understand the genetic risk profile of breast cancer in this population. Methods: A prospective case-control study was conducted involving 45 breast cancer patients and 51 controls recruited from four major hospitals. DNA was extracted from blood samples, followed by targeted sequencing of BRCA1/2 exonic and intronic regions using the Ampliseq BRCA panel and Illumina MiSeq platform. Variant calling was performed, clinical significance was evaluated on ClinVar and BRCA Exchange databases, and haplotype analysis was performed using NIH LDlink and Haploview 4.2 software. Results: Pathogenic BRCA1/2 variants were identified in 6.7% of breast cancer patients, all with TNBC and a family history of cancer. Two pathogenic BRCA1 variants were detected: a frameshift deletion BRCA1 c.133_134delAA (p.Lys45 fs) (rs397508857) and a missense variant BRCA1 c.5324T >A (p.Met1775Arg) (rs41293463). A BRCA2 frameshift deletion BRCA2 c.8817_8820del (p.Lys2939 fs) (rs397508010) was also identified. These variants were absent in controls. Haplotype analysis revealed distinct BRCA1 and BRCA2 haplotypes in the breast cancer group. Conclusion: This study identifies key BRCA1/2 pathogenic variants and unique haplotypes in Nigerian breast cancer patients, highlighting the need for population-specific genetic screening. Integrating genetic testing into breast cancer management strategies could facilitate early detection, personalized treatment planning, and genetic counseling in Nigeria.
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    Frequency Of BRCA1 Polymorphisms (rs799917 and rs1799966) Among Nigerian Breast Cancer Patients
    (Covenant University Ota, 2025-03) OGUNNIYI, OLUWABUSAYO BUNMI; Covenant University, Dissertation
    Breast cancer (BCa) is the most diagnosed malignancy among women worldwide, with an estimated 2.3 million new cases and 666,103 deaths recorded in 2022. In Nigeria, BCa remains the leading cause of cancer-related mortality among women, accounting for 32,278 (25.3%) new cases and 16,322 (20.5%) deaths in 2022. Breast cancer gene 1 (BRCA1) is a tumour suppressor gene involved in DNA damage repair, cell cycle regulation, and maintenance of genome stability. Studies suggest that genetic factors, such as Single Nucleotide Polymorphism (SNPs) in the BRCA1 genes, play a pivotal role in the development of cancers. The BRCA1 gene harbors specific SNPs within its coding sequence, including rs799917 and rs1799966. These SNPs interfere with the interaction between BRCA1 mRNA and miR-638, significantly decreasing BRCA1 expression among individuals carrying these variants. Several studies have reported correlations between BRCA1 polymorphisms rs799917 and rs1799966 with the risk of BCa. However, this relationship remains controversial. This study assesses the frequency of BRCA1 rs799917 and rs1799966 polymorphisms and their association with BCa in Nigeria. The case-control study included 500 BCa patients and 200 paired healthy controls. TaqMan genotyping assay was used to determine the genotypes of rs799917 and rs1799966 polymorphisms. Using logistic regression and Pearson's chi-square test, a statistically significant difference (p < 0.05) was identified in the genotype frequencies. The G allele of rs799917(p= 0.017; OR: 1.39) showed significant associations with the risk of breast cancer in Nigeria and, while globally reported as the wild-type allele, is observed as the variant allele in our population. The C Allele of rs1799966 confers a protective risk against breast cancer. Further study should focus on functional genomics to evaluate the interaction between miR-638 and the mRNA in individuals carrying this SNP, particularly in the Nigerian population. Keywords: breast