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<p>Prostate adenocarcinoma (PRAD) remains a leading cause of cancer-related mortality in men, highlighting an urgent need to identify novel prognostic biomarkers and therapeutic targets. While the role of solute carrier family genes in tumorigenesis has become increasingly well-defined, the function of the transmembrane transporter SLC45A2 in PRAD progression and immune regulation remains unclear. Transcriptomic data from 499 PRAD tumors and 52 normal tissues in the TCGA-PRAD database were integrated. Differentially expressed genes were screened using DESeq2, and independent prognostic genes were identified via Cox regression analysis (adjusted for age, TNM stage, and metastasis status). The expression of SLC45A2 in PRAD cell lines was verified by qRT-PCR and Western blot. CCK-8, wound-healing, and Transwell assays were performed to evaluate the effects of SLC45A2 on cell proliferation and migration. The infiltration levels of 24 immune cell types were analyzed using the ssGSEA algorithm. IHC and HPA database validated tissue-level protein expression. In vivo experiment was xenograft tumor model. The immunomodulatory role of SLC45A2 was explored via co-culture experiments of DU145 cells and CD8⁺T cells. SLC45A2 was identified as an independent prognostic factor for PRAD. Its mRNA and protein levels were significantly upregulated in tumor tissues compared to normal tissues. Functional experiments showed that SLC45A2 knockdown inhibited the proliferation and migration of LNCaP and DU145 cells, while SLC45A2 overexpression reversed these effects. Mechanistically, SLC45A2 promoted PRAD cell proliferation by activating the PI3K/AKT pathway and mediated immune evasion by impairing the cytotoxic effect of CD8⁺T cells. SLC45A2 drives PRAD progression via dual oncogenic mechanisms: direct promotion of tumor proliferation and migration, and suppression of cytotoxic immune cell infiltration, confirming that SLC45A2 can serve as a potential prognostic biomarker and therapeutic target for advanced PRAD.</p>

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SLC45A2 drives prostate cancer progression through tumor promotion and immune suppression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Run Tang,
  • Cheng Wang,
  • Yingxiang Zhu,
  • Kai Liu,
  • Zeming Wu

摘要

Prostate adenocarcinoma (PRAD) remains a leading cause of cancer-related mortality in men, highlighting an urgent need to identify novel prognostic biomarkers and therapeutic targets. While the role of solute carrier family genes in tumorigenesis has become increasingly well-defined, the function of the transmembrane transporter SLC45A2 in PRAD progression and immune regulation remains unclear. Transcriptomic data from 499 PRAD tumors and 52 normal tissues in the TCGA-PRAD database were integrated. Differentially expressed genes were screened using DESeq2, and independent prognostic genes were identified via Cox regression analysis (adjusted for age, TNM stage, and metastasis status). The expression of SLC45A2 in PRAD cell lines was verified by qRT-PCR and Western blot. CCK-8, wound-healing, and Transwell assays were performed to evaluate the effects of SLC45A2 on cell proliferation and migration. The infiltration levels of 24 immune cell types were analyzed using the ssGSEA algorithm. IHC and HPA database validated tissue-level protein expression. In vivo experiment was xenograft tumor model. The immunomodulatory role of SLC45A2 was explored via co-culture experiments of DU145 cells and CD8⁺T cells. SLC45A2 was identified as an independent prognostic factor for PRAD. Its mRNA and protein levels were significantly upregulated in tumor tissues compared to normal tissues. Functional experiments showed that SLC45A2 knockdown inhibited the proliferation and migration of LNCaP and DU145 cells, while SLC45A2 overexpression reversed these effects. Mechanistically, SLC45A2 promoted PRAD cell proliferation by activating the PI3K/AKT pathway and mediated immune evasion by impairing the cytotoxic effect of CD8⁺T cells. SLC45A2 drives PRAD progression via dual oncogenic mechanisms: direct promotion of tumor proliferation and migration, and suppression of cytotoxic immune cell infiltration, confirming that SLC45A2 can serve as a potential prognostic biomarker and therapeutic target for advanced PRAD.