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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1503623

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

Provisionally accepted
Yusong Zhou Yusong Zhou 1Shiwei Huang Shiwei Huang 1Bing Yang Bing Yang 2Jing Tan Jing Tan 1Zhun Zhang Zhun Zhang 1Wei Liu Wei Liu 1*
  • 1 Third Xiangya Hospital, Central South University, Changsha, China
  • 2 Zunyi Medical University, Zunyi, Guizhou Province, China

The final, formatted version of the article will be published soon.

    Background Anoikis 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. Methods: Anoikis-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.One 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.Based 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.

    Keywords: Anoikis, BLCA, Rac3, prognosis, immune microenvironment

    Received: 29 Sep 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Zhou, Huang, Yang, Tan, Zhang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Wei Liu, Third Xiangya Hospital, Central South University, Changsha, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.