Subrata Pramanik

Bio: Subrata Pramanik is an academic researcher from Örebro University. The author has contributed to research in topics: DNA repair & Genome editing. The author has co-authored 1 publications.

Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing.

Abstract: Family with sequence similarity 72 A (FAM72A) is a pivotal mitosis-promoting factor that is highly expressed in various types of cancer. FAM72A interacts with the uracil-DNA glycosylase UNG2 to prevent mutagenesis by eliminating uracil from DNA molecules through cleaving the N-glycosylic bond and initiating the base excision repair pathway, thus maintaining genome integrity. In the present study, we determined a specific FAM72A-UNG2 heterodimer protein interaction using molecular docking and dynamics. In addition, through in silico screening, we identified withaferin B as a molecule that can specifically prevent the FAM72A-UNG2 interaction by blocking its cell signaling pathways. Our results provide an excellent basis for possible therapeutic approaches in the clinical treatment of cancer.

Analeptic activity of 2-Hydroxyl-5-Nitrobenzaldehyde: Experimental, DFT studies, and in silico molecular docking approach

Abstract: This study was carried out to evaluate the spectroscopic, molecular properties, and in silico biological assessment of 2-Hydroxyl-5-Nitrobenzaldehyde (NSA) characterized by FT-IR, UV, NMR spectral, and first-principle density functional theory (DFT). The optimized molecular geometry, the vibrational wavenumbers, and infrared intensities activities were calculated by using the density functional theory (DFT) B3LYP method with a 6–311++G(d,p) basis set. The detailed interpretation of the vibrational spectra was assigned by VEDA program. The results of NBO analysis show that LP(3)O12 and LP(2)O13 bonding orbitals participated as donors and the π*N10–O11 and π*C2–C3 antibonding orbitals as acceptors in all the four phases understudy with occupancies in the range of 1.45453, 1.85287 leading to the stabilization energy of 160.60 and, 30.55 kcal/mol, which results in intramolecular charge transfer leading to the stabilization of the molecule. Moreover, Drug likeness properties of NSA are predicted. The predicted ADMET properties showed high gastrointestinal absorption, does not permeant the brain–blood barrier, nor any Cytochrome P450 inhibition (1A2, 2C19, 2C9, 2DA, 3A4, and 3A4) without violating any of the Lipinski rules. The result from the molecular docking showed that NSA has the highest negative mean binding affinity of −5.71 kcal/mol, followed by CFN and EDE which are approximately equal at −5.176 and −5.004 kcal/mol respectively and added to a more significant hydrogen bond with amino acids residues of the selected receptor proteins. Therefore, it could be said that NSA is a potential analeptic agent.

Integrated systemic analysis of FAM72A to identify its clinical relevance, biological function, and relationship to drug sensitivity in hepatocellular carcinoma

Abstract: Background The family with sequence similarity 72 member A (FAM72A) protein has been identified as an effector of multiple pathological processes in many cancers. The value of FAM72A in HCC remains largely unknown. Methods Data from TCGA-LIHC, ICGC-LIRI-JP, IMvigor210, cBioPortal, GeneMANIA, and TIMER were processed and visualized to explore the association between FAM72A and the prognosis, stemness phenotype, mutational burden, immune cell infiltration, and drug sensitivity in HCC patients. Potential pathways were also revealed. Furthermore, we experimentally verified the results in vivo and in vitro using immunohistochemistry, western blotting, and CCK-8 assays. Results First, FAM72A mRNA expression was significantly upregulated in HCC. High FAM72A expression was independently associated with a poor prognosis. Experimental validation confirmed that FAM72A was remarkably overexpressed in HCC patients and mice. Moreover, FAM72A knockdown suppressed HCC cell proliferation. In addition, the frequency of TP53 mutations was significantly higher in the high FAM72A expression group. Subsequently, the enrichment analysis revealed that FAM72A was closely related to immune processes and mTOR pathways. Silencing FAM72A increased the expression levels of mTOR in HCC cell lines. The FAM72A-mTOR pathway was strongly associated with a poor prognosis for patients with HCC. Patients with high FAM72A expression levels might be more resistant to sorafenib. Furthermore, the expression of FAM72A and mTOR was significantly associated with the abundance of some tumor-infiltrating immune cells, especially CD4+ T cells. Finally, patients with high levels of FAM72A and mTOR were more sensitive to immunotherapy. Conclusions FAM72A, a member of the FAM72 family, might be a prognostic and immunotherapeutic target for HCC patients.

RNA sequencing and bioinformatics analysis revealed PACSIN3 as a potential novel biomarker for platinum resistance in epithelial ovarian cancer

Abstract: Failure to respond to treatment in epithelial ovarian cancer can often be attributed to platinum‐based chemotherapy resistance. However, the possible mechanisms or candidate biomarkers associated with platinum resistance are yet to be elucidated, even though many researchers have performed related studies.