Background Exonuclease 1 (EXO1) has been identified to be highly expressed in different human malignancies, but its expression and prognostic role in lung adenocarcinoma (LUAD) remain unknown. Materials and Methods Two independent cohorts extracted from public databases and one cohort from our center were analyzed in this study. Expression levels of EXO1 in LUAD tissues and paired para-cancer tissues were detected. The prognostic value of EXO1 in LUAD patients was evaluated in the three cohorts. Enrichment analyses were performed to explore the possible underlying biological pathways. Moreover, we also explored the correlations between EXO1 and tumor-infiltrating immune cells and evaluated the impact of EXO1 knock-down on the migration of lung cancer cells. Results In this study, we found that EXO1 was highly expressed in LUAD tissues compared with para-cancerous tissues in public databases ( p < 0.01), which was consistent with our data ( p < 0.01). Survival analysis indicated that high expression of EXO1 was associated with poor prognosis in LUAD ( p < 0.01). Enrichment analyses indicated that biological pathways like cell cycle regulation, DNA damage and repair, immune response, neuroactive ligand-receptor interaction, may be associated with EXO1 aberrant expression. Moreover, high expression of EXO1 was correlated with decreased infiltrating B cells ( p < 0.01) and CD4+ T cells ( p < 0.01) levels, and low infiltrating levels of B cells ( p < 0.01) and dendritic cells (DCs) ( p < 0.05) indicated poor overall survival (OS) in LUAD. Additionally, in vitro experiments suggested that knockdown of EXO1 may inhibit the migratory ability of lung cancer cells. Conclusion In conclusion, EXO1 is a potential prognostic biomarker in LUAD, and correlates with infiltrating levels of immune cells in the tumor microenvironment. Further prospective validation of EXO1 in lung cancer is warranted.
Brain metastasis is a leading cause of death worldwide, but the mechanism involved remains unclear. Stromal cell‐derived factor‐1 (SDF‐1)/C‐X‐C motif chemokine receptor 4 (CXCR4) signaling has been reported to induce the directed metastasis of cancers, and adenosine A2A receptor activation suppresses the SDF‐1/CXCR4 interaction. However, whether A2A receptor activation implicates the SDF‐1/CXCR4 signaling pathway and thus modulates brain metastasis remains unclear. In this study, Western blot was performed to evaluate the protein levels. Cell invasion and migration assays were used to estimate the metastasis ability of PC‐9 cells. The viability of cells was demonstrated by lactate dehydrogenase and cell proliferation assays. And the findings in vitro were further identified in nude mice. Notably, adenosine A2A receptor activation inhibited the proliferation and viability of PC‐9 cells and thus suppressed the brain metastasis. A2A receptor stimulation protected the function of blood‐brain barrier (BBB). The suppression of brain metastasis and the protection of BBB by A2A receptor relied on SDF‐1/CXCR4 signaling, and treatment using A2A receptor agonist and CXCR4 antagonist protected the nude mice from malignancy metastasis in vivo. Adenosine A2A receptor activation suppressed the brain metastasis by implicating the SDF‐1/CXCR4 axis and protecting the BBB.
Kinesin superfamily protein 3C (KIF3C), a motor protein of the kinesin superfamily, is expressed in the central nervous system (CNS). Recently, several studies have suggested that KIF3C may act as a potential therapeutic target in solid tumors. However, the exact function and possible mechanism of the motor protein KIF3C in glioma remain unclear. In this study, a variety of tests including CCK-8, migration, invasion, and flow cytometry assays, and western blot were conducted to explore the role of KIF3C in glioma cell lines (U87 and U251). We found that overexpression of KIF3C in glioma cell lines promoted cell proliferation, migration, and invasion and suppressed apoptosis, while silencing of KIF3C reversed these effects. Ectopic KIF3C also increased the expression of N-cadherin, vimentin, snail, and slug to promote the epithelial-mesenchymal transition (EMT). Mechanistically, overexpression of KIF3C increased the levels of phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT). These responses were reversed by KIF3C downregulation or AKT inhibition. Our results indicate that KIF3C promotes proliferation, migration, and invasion and inhibits apoptosis in glioma cells, possibly by activating the PI3K/AKT pathway in vitro. KIF3C might act as a potential biomarker or therapeutic target for further basic research or clinical management of glioma.
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