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Oncogenic GBX2 promotes the malignant behaviors of bladder cancer cells by binding to the ITGA5 promoter and activating its transcription

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Abstract

In bladder cancer patients, metastasis after surgical resection and serious adverse reactions brought by cisplatin-based systemic chemotherapy make it urgent to explore novel therapeutic methods for improving the clinical outcomes of patients with unsuccessful first-line chemotherapy and disease progression. In this study, GBX2 has been recognized as a differentially expressed transcriptional factor between bladder cases with response to treatment and progressive disease based on online expression profile analysis. Higher GBX2 expression was correlated with poorer OS, DSS, and PFS in bladder cancer patients. GBX2 co-expressed genes were enriched in ECM regulation. ITGA5 was positively correlated with GBX2. GBX2 and ITGA5 were notably elevated in bladder cancer cells. GBX2 and ITGA5 similarly affected bladder cancer cell phenotypes via facilitating cell viability, migration, and invasion. By binding to the promoter region of ITGA5, GBX2 activated ITGA5 transcription, upregulating ITGA5 expression. In bladder cancer cells co-transfected with sh-GBX2 and ITGA5 oe, the inhibitory effects of GBX2 knockdown on bladder cancer cell malignant behaviors were partially eliminated by ITGA5 overexpression. In conclusion, GBX2 and ITGA5 serve as oncogenic factors, promoting the viability, migration, and invasion of bladder cancer cells. GBX2 exerts its functions by targeting the ITGA5 promoter region to activate ITGA5 transcription.

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Funding

This study was supported by National Natural Science Foundation of China (No. 81802561) and Natural Science Foundation of Hunan Province, China (No. 2019JJ50977).

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Authors and Affiliations

  1. Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Yaoyao Xiong, Xiongbing Zu, Minfeng Chen, Wei He & Lin Qi

  2. Extracorporeal Life Support Center of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Yaoyao Xiong

  3. Department of Urology, Turpan People’s Hospital, Turpan, 838000, Xinjiang, China

    Xiaohang Song &  Kudusi

Authors
  1. Yaoyao Xiong
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  2. Xiaohang Song
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  3. Kudusi
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  4. Xiongbing Zu
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  5. Minfeng Chen
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  6. Wei He
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  7. Lin Qi
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Correspondence to Wei He.

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Fig. S1

Images for Wound healing and Transwell assays performed on bladder cancer cells transfected with sh-GBX2 or GBX2 oe. (PNG 7625 kb)

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Fig. S2

Images for Wound healing and Transwell assays performed on bladder cancer cells transfected with sh-ITGA5 or ITGA5 oe. (PNG 6612 kb)

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Fig. S3

Images for Transwell assays performed on bladder cancer cells co-transfected with sh-GBX2 and ITGA5 oe. (PNG 2903 kb)

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Xiong, Y., Song, X., Kudusi et al. Oncogenic GBX2 promotes the malignant behaviors of bladder cancer cells by binding to the ITGA5 promoter and activating its transcription. Funct Integr Genomics 22, 937–950 (2022). https://doi.org/10.1007/s10142-022-00870-8

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  • DOI: https://doi.org/10.1007/s10142-022-00870-8

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