Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis

BACKGROUND The regulatory effects of KIF26B on gastric cancer(GC)have been confirmed,but the specific mechanism still needs further exploration.Pan-cancer analysis shows that the KIF26B expression is highly related to immune infiltration of cancerassociated fibroblasts(CAFs),and CAFs promote macrophage M2 polarization and affect cancers’progression.AIM To investigate the regulatory functions of KIF26B on immune and metastasis of GC.METHODS We analyzed genes’mRNA levels by quantitative real-time polymerase chain reaction.Expression levels of target proteins were detected by immunohistochemistry,ELISA,and Western blotting.We injected AGS cells into nude mice for the establishment of a xenograft tumor model and observed the occurrence and metastasis of GC.The degree of inflammatory infiltration in pulmonary nodes was observed through hematoxylin-eosin staining.Transwell and wound healing assays were performed for the evaluation of cell invasion and migration ability.Tube formation assay was used for detecting angiogenesis.M2-polarized macrophages were estimated by immunofluorescence and flow cytometry.RESULTS KIF26B was significantly overexpressed in cells and tissues of GC,and the higher expression of KIF26B was related to GC metastasis and prognosis.According to in vivo experiments,KIF26B promoted tumor formation and metastasis of GC.KIF26B expression was positively associated with CAFs’degree of infiltration.Moreover,CAFs could regulate M2-type polarization of macrophages,affecting GC cells’migration,angiogenesis,invasion,and epithelial-mesenchymal transition process.CONCLUSION KIF26B regulated M2 polarization of macrophage through activating CAFs,regulating the occurrence and metastasis of GC.

ERF4 interacts with and antagonizes TCP15 in regulating endoreduplication and cell growth in Arabidopsis

Endoreduplication is prevalent during plant growth and development,and is often correlated with large cell and organ size.Despite its prevalence,the transcriptional regulatory mechanisms underlying the transition from mitotic cell division to endoreduplication remain elusive.Here,we characterize ETHYLENE-RESPONSIVEELEMENTBINDING FACTOR 4(ERF4)as a positive regulator of endoreduplication through its function as a transcriptional repressor.ERF4 was specifically expressed in mature tissues in which the cells were undergoing expansion,but was rarely expressed in young organs.Plants overexpressing ERF4 exhibited much larger cells and organs,while plants that lacked functional ERF4 displayed smaller organs than the wild-type.ERF4 was further shown to regulate cell size by controlling the endopolyploidy level in the nuclei.Moreover,ERF4 physically associates with the class I TEOSINTE BRANCHED 1/CYCLOIDEA/PCF(TCP)protein TCP15,a transcription factor that inhibits endoreduplication by activating the expression of a key cell-cycle gene,CYCLIN A2;3(CYCA2;3).A molecular and genetic analysis revealed that ERF4promotes endoreduplication by directly suppressing the expression of CYCA2;3.Together,this study demonstrates that ERF4 and TCP15 function as a module to antagonistically regulate each other?s activity in regulating downstream genes,thereby controlling the switch from the mitotic cell cycle to endoreduplication during leaf development.These findings expand our understanding of how the control of the cell cycle is fine-tuned by an ERF4–TCP15 transcriptional complex.