Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Distant metastasis is a primary cause of mortality in prostate cancer (PCa).
• The precise role of exosomal long noncoding RNAs (lncRNAs) in PCa metastasis remains incompletely understood.
• Identifying novel mechanisms and biomarkers for PCa metastasis is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate the role of exosomal lncRNA HOXD-AS1 in prostate cancer metastasis.
• To elucidate the underlying molecular mechanisms by which exosomal HOXD-AS1 influences PCa cell behavior.
• To evaluate the potential of serum exosomal HOXD-AS1 as a diagnostic and prognostic biomarker for metastatic PCa.

Main Methods:

• Quantification of exosomal HOXD-AS1 in castration-resistant PCa (CRPC) cell lines and serum from metastatic PCa patients.
• In vitro and in vivo experiments to assess the effect of exosomal HOXD-AS1 on PCa cell metastasis.
• Mechanistic studies involving exosome internalization, competing endogenous RNA (ceRNA) assays, and analysis of the miR-361-5p/FOXM1 axis.
• Correlation analysis of serum exosomal HOXD-AS1 levels with clinical parameters such as Gleason Score, metastasis, and survival rates.

Main Results:

• Exosomal HOXD-AS1 was found to be upregulated in CRPC cell lines and serum from metastatic PCa patients, correlating with tissue expression.
• Exosomal HOXD-AS1 was confirmed to promote PCa cell metastasis both in vitro and in vivo by inducing a metastatic phenotype.
• Mechanistically, exosomal HOXD-AS1 acts as a ceRNA, modulating the miR-361-5p/FOXM1 axis to drive PCa metastasis.
• Serum exosomal HOXD-AS1 levels were significantly elevated in metastatic PCa patients, particularly those with high-volume disease, and correlated with Gleason Score, metastasis, and survival outcomes (PSA recurrence-free survival and progression-free survival).

Conclusions:

• Exosomal HOXD-AS1 plays a significant role in promoting prostate cancer distant metastasis via the miR-361-5p/FOXM1 pathway.
• Serum exosomal HOXD-AS1 represents a promising and novel liquid biopsy biomarker for the detection and management of metastatic prostate cancer.
• These findings offer new insights into the molecular regulation of PCa metastasis and highlight potential therapeutic targets.