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- W3118839188 abstract "Abstract Background : As small GTP-binding proteins, ARL family members (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. Methods : The expression status, interactive relations, potential pathways and genetic variations of ARLs are analyzed by bioinformatics tools. Machine learning models and enrichment analysis are performed by R platform. The biological functions of ARL4C are demonstrated by in vitro and in vivo experiments. The nomogram is further constructed to validate the prognostic value of ARL4C for GC patients. Results : ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant diagnostic and prognostic indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably reverses the epithelial-mesenchymal transition (EMT) and inhibits the growth and metastasis of GC cells both i n vitro and in vivo . Moreover, enrichment analysis indicates that TGF-β1 is highly correlated with ARL4C, while ARL4C-related genes are significantly enriched in the TGF-β1 signaling. Correspondingly, we demonstrate that TGF-β1 treatment dramatically increases ARL4C expression, and ARL4C knockdown reverses TGF-β1-induced EMT possibly by inhibiting the expression of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients both in Kaplan-Meier analysis and nomogram model. Conclusion: Our work is of significance for comprehensively understanding the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients." @default.
- W3118839188 created "2021-01-18" @default.
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- W3118839188 date "2020-06-18" @default.
- W3118839188 modified "2023-10-14" @default.
- W3118839188 title "ARL4C is A Key Driver of Gastric Cancer: An Integrative Analysis of ARL Family Members" @default.
- W3118839188 doi "https://doi.org/10.21203/rs.3.rs-35982/v1" @default.
- W3118839188 hasPublicationYear "2020" @default.
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