Expression and functional analysis of CDH11 and CDH22 in low-grade glioma
TL;DR
It is demonstrated that CDH11 knockdown and CDH22 overexpression notably suppressed the proliferation, migration and invasion of LGG cells, and such pro-tumor effects could be attenuated by CDH11 silencing or CDH22 overexpression.
Abstract
Low-grade glioma (LGG) is a heterogeneous central nervous system tumor with limited reliable prognostic biomarkers and targeted therapeutic strategies. The roles of cadherin superfamily members CDH11 and CDH22 in LGG pathogenesis and progression remain poorly elucidated. Herein, we comprehensively explored their expression profiles, prognostic significance, biological behaviors, and immune correlation in LGG using multi-omics bioinformatics analysis based on GEPIA, cBioPortal, TIMER and LinkedOmics databases, combined with partial in vitro functional validation using SW1783 and HS683 cell lines. We performed siRNA-mediated CDH11 knockdown and plasmid-mediated CDH22 overexpression, and applied CCK-8, wound-healing and Transwell assays to assess cell proliferation, migration and invasion. A Transwell co-culture model of LGG cells and THP-1-derived M2 macrophages was further established to investigate the crosstalk between tumor cells and tumor-associated macrophages. Bioinformatics results showed that CDH11 was upregulated while CDH22 was downregulated in LGG versus normal brain tissues. High CDH11 and low CDH22 expression were both correlated with unfavorable overall and disease-free survival. Genetic alterations of the two genes occurred in about 5% of LGG cases, mainly manifested as dysregulated mRNA expression. CDH11 expression was positively correlated with the infiltration of multiple immune cells and immune scores in LGG, whereas CDH22 showed a distinct correlation tendency. Functional enrichment analysis revealed different pathway characteristics between CDH11 and CDH22: CDH11 was enriched in actin cytoskeleton organization and cell adhesion, while CDH22 was mainly involved in immune activation and cell cycle regulation. In vitro functional experiments demonstrated that CDH11 knockdown and CDH22 overexpression notably suppressed the proliferation, migration and invasion of LGG cells. M2 macrophages significantly enhanced the malignant phenotypes of LGG cells, and such pro-tumor effects could be attenuated by CDH11 silencing or CDH22 overexpression. In summary, CDH11 and CDH22 display distinct expression patterns, prognostic implications and immune associations in LGG.