Frontiers in Pharmacology (Nov 2024)

Role of anoikis-related gene RAC3 in prognosis, immune microenvironment, and contribution to malignant behavior in vitro and in vivo of bladder urothelial carcinoma

  • Yusong Zhou,
  • Shiwei Huang,
  • Bing Yang,
  • Jing Tan,
  • Zhun Zhang,
  • Wei Liu

DOI
https://doi.org/10.3389/fphar.2024.1503623
Journal volume & issue
Vol. 15

Abstract

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BackgroundAnoikis disrupts the normal apoptotic process in cells, leading to abnormal proliferation and migration, thereby promoting tumor formation and development. However, the role of anoikis in bladder urothelial carcinoma (BLCA) still requires further exploration.MethodsAnoikis-related genes (ARGs) were retrieved from the GeneCards and Harmonizome databases to distinguish various subtypes of BLCA and develop a predictive model for BLCA. The immune microenvironment and enrichment pathways between various subtypes were also analyzed using consensus clustering. Potential medications were screened by utilizing drug sensitivity analysis. In vitro and vivo, the character of the independent prognostic gene in BLCA was confirmed through cell studies and mouse xenograft models.ResultsOne hundred thirty differentially expressed genes (DEGs) were identified, and nine of them were chosen to construct predictive models that can accurately forecast the prognosis of BLCA patients. K = 2 was correctly identified as the optimal clustering type for BLCA, showing prominent differences in survival rates between the two subgroups. The immune-related functional studies manifested that the two subtypes’ immune cell expressions differed. It was verified that RAC3 is an independent prognostic gene for BLCA. RAC3 shows high expression levels in BLCA, as indicated by its consistent mRNA and protein levels across different gene expressions. The functional verification results of RAC3 in BLCA showed that silencing RAC3 can significantly inhibit BLCA cell proliferation, colony formation, and migration. RAC3 knockdown inhibited the growth and migration of BLCA in vivo. SB505124 exhibited a significant inhibitory effect on the proliferation of BLCA cells.ConclusionBased on the predictive model developed in this study, BLCA patients’ prognoses can be accurately predicted. SB505124 could become an important drug in the treatment of BLCA patients. RAC3 is essential in prognosis, immune microenvironment, and malignant behavior of BLCA in vitro and in vivo. It will also offer the potential for personalized treatment for BLCA patients and generate new research avenues for clinical investigators.

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