The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments.

The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is a medicinal herb with anticancer properties. Expression of EpCAM and its downstream target genes (Myc and TERT) wasdownregulated upon treatment with costunolide in Jurkat cells. A significant change in the telomere length of Jurkat cells was not noted at 72 h of costunolide treatment. An in silico study revealed hydrophobic interactions between EpCAM extracellular domain and Myc bHLH with costunolide. Reduced expression of NFκB, a transcription factor of EpCAM, Myc, and TERT in costunolide-treated Jurkat cells, suggested that costunolide inhibits gene expression by targeting NFκB and its downstream targets. Overall, the study proposes that costunolide could be a promising therapeutic biomolecule for leukemia.

Background Head and neck squamous cell carcinoma (HNSC) stand as one of the most fatal malignancies worldwide. The intricate nature of this disease has contributed to a limited understanding of its diagnostic and prognostic indicators. This study comprehensively investigated the dysregulation of PIAS family genes (PIAS1, PIAS2, PIAS3, and PIAS4) in Head and Neck Squamous Cell Carcinoma (HNSC). Methods Cell culturing, RT-qPCR, bisulfite sequencing, UALCAN, GEPIA, Human Protein Atlas (HPA), MEXPRESS, cBioPortal, Prognostic model development, DAVID, TISCH2, cell culture, gene knockdown, cell culture, colony formation, wound healing, DrugBank, and molecular docking analyses. Results RT-qPCR demonstrated significant up-regulation of PIAS1, PIAS2, PIAS3, and PIAS4 in HNSC cell lines. ROC curve analysis indicated high diagnostic accuracy for these genes. Promoter methylation analysis revealed a negative correlation, suggesting hypomethylation as a potential mechanism for their overexpression. Validation across multiple datasets and immunohistochemistry supported their up-regulation in HNSC. Mutational analysis showed low mutation frequencies in PIAS1, PIAS2, PIAS3, and PIAS4 genes. Survival analysis implicated elevated PIAS expression in poorer overall survival of HNSC patients, and a prognostic model demonstrated predictive robustness. Correlation with immune cells highlighted associations of PIAS gene with various immune cell types. GO and KEGG analyses unveiled functional involvement of PIAS genes in critical cellular processes and signaling pathways. Functional assays demonstrated that PIAS knockdown inhibited HNSC cell proliferation, migration, and invasion. Lastly, the identification of Cyclocreatine and Vorinostat as potential inhibitors through drug acquisition and molecular docking provides insights into therapeutic avenues for HNSC patients. Conclusion These findings contribute to the understanding of PIAS family genes in HNSC pathogenesis, diagnosis, prognosis, and potential therapeutic targeting.