Menaquinones (MKs), known mainly as respiratory quinones in bacteria, are found in the majority of bacterial species and show great variety as regards to the structure, i.e. the length of the side-chain, its saturation, ring methylation and other modifications. MK function in bacteria is attributed mainly to its function in anaerobic respiration, but the number of potential electron donors and acceptors is very numerous. However, their function is far beyond contribution in respiration. For example, they take part in bacterial photosynthesis, mediate extracellular electron transport or participate in cellular signalling. Moreover, respiratory MK pool of bacteria, is an electron acceptor from DsbA-DsbB two-component system engaged in the formation of disulfide bridges in various target proteins. The classical and a new MK biosynthetic pathway in bacteria, so-called futalosine pathway, have been recently thoroughly characterized and nearly all the enzymatic steps recognized, showing in some cases unusual catalytic mechanisms. Finally, examples of the analytical methods of MKs determination are presented, including practical hints.
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with dismal clinical outcomes, and how cellular senescence modulates ESCC biology remains poorly understood. Here, we integrated transcriptomic profiles from the TCGA-ESCC cohort with a curated panel of cellular senescence-related genes to identify and functionally validate senescence-associated regulators in ESCC. Univariate Cox regression and consensus clustering stratified ESCC patients into two molecular subtypes with divergent survival. Through differential expression analysis, random forest prioritization, and independent validation in the GSE20347 cohort, we identified GREM2 and PIK3C2G as lead candidate genes. Both were consistently downregulated in ESCC tumors and cell lines, and low expression predicted poorer overall survival. Gain-and loss-of-function experiments demonstrated that GREM2 and PIK3C2G drive p16/p21-dependent cellular senescence, trigger the senescence-associated secretory phenotype (SASP), and restrict proliferation in esophageal epithelial cells. Immune correlation analyses linked both genes to immune cell infiltration, chemokine signaling, and MHC molecule expression in the tumor microenvironment. These findings establish GREM2 and PIK3C2G as senescence-associated tumor suppressors in ESCC, offering candidate biomarkers and a rationale for exploring senescence-directed therapies in this disease.
