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TRAIP suppressed apoptosis and cell cycle to promote prostate cancer proliferation via TRAF2–PI3K–AKT pathway activation

  • Urology - Original Paper
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Abstract

Background

TRAF-interacting protein (TRAIP) is a RING-type E3 ubiquitin ligase, which has been implicated in various cellular processes and participated in various cancers as an oncogene. However, the function and potential mechanism of TRAIP in prostate cancer (PCa) have not been investigated so far.

Methods

Public TGCA data were used to evaluate the expression profile of TRAIP in prostatic tumors. The relative expression of TRAIP and TRAF2 in PCa tissues and tumor cell lines was detected by qPCR, western blot, and IHC staining. Next, TRAIP knockdown and overexpression plasmids were constructed and transfected into PCa cell lines. Moreover, cell proliferation, invasion, migration, and apoptosis were measured by colony formation, Transwell, wound healing, and flow cytometry assays. Subsequently, cell cycle and signaling pathway-related proteins were tested by western blot. Finally, the effect of TRAIP on PCa was measured based on the nude mouse xenograft model.

Results

TRAIP was significantly upregulated in PCa tissues and tumor cell lines. In addition, TRAIP promoted cell proliferation, invasion, and migration of PCa cell lines. Such an oncogenic property was mediated by the cell cycle arrest and the inhibition of apoptosis, as indicated by different functional assays and the expression of cell cycle and apoptosis regulatory proteins in cultured cells. Moreover, TRAIP combined with TRAF2 to activate PI3K/AKT pathway. Finally, TRAIP depletion suppressed the growth of tumors and cell proliferation in vivo.

Conclusions

Our study first revealed that TRAIP promoted tumor progression and identified it as a potential therapeutic target for PCa patients in the future.

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Data availability

The authors declare that all data supporting the findings of this study are available within the paper, and any raw data can be obtained from the corresponding author upon request.

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Authors and Affiliations

  1. Department of Urology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, China

    Yuan Gu & Chaozhao Liang

  2. Department of Urology, Anhui Second People’s Hospital, Hefei, 230041, Anhui, China

    Yuan Gu

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  1. Yuan Gu
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Contributions

YG and CL designed the experiments, carried them out, analyzed and interpreted the data, and prepared the manuscript. All authors have read and approved the manuscript.

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Correspondence to Chaozhao Liang.

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Gu, Y., Liang, C. TRAIP suppressed apoptosis and cell cycle to promote prostate cancer proliferation via TRAF2–PI3K–AKT pathway activation. Int Urol Nephrol 56, 1639–1648 (2024). https://doi.org/10.1007/s11255-023-03890-w

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