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Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression

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Abstract

Prostate cancer (PCa) is a prevalent malignant neoplasm affecting the male reproductive system globally. However, the diagnostic and therapeutic approaches fall short of meeting the demands posed by PCa. Poor expression of miRNA-203 (miR-203) within PCa tissues and cells implies its potential utility as a diagnostic indicator for PCa. Exosomes (Exo), membranous vesicles released by various cells, are rich reservoirs of miRNAs. However, the presence of miR-203 presents within Exo derived from PCa cells remains unclarified. In this study, Exo was isolated from urine specimens collected from clinical PCa patients and LNCaP cells to detect miR-203 expression. Meanwhile, the impact of overexpressed miR-203 on M0 macrophages (mø) was analyzed. Subsequently, alterations in the proliferative, migratory, and invasive capacities of LNCaP cells were examined within a co-culture system featuring elevated miR-203 levels in both macrophages and LNCaP cells. Furthermore, the repercussions of miR-203 upregulation or inhibition were explored in a murine PCa tumor model. The results revealed that Exo manifested a circular or elliptical morphology, encapsulating a phospholipid bilayer approximately 100 nm in diameter. Notably, Exo readily infiltrated, with both Exo and miR-203-overexpressing Exo prompting macrophage polarization toward the M1 subtype. In the co-culture system, miR-203 exhibited pronounced suppression of LNCaP cell proliferation, migration, and invasion, while concurrently fostering apoptosis as compared with the LNCaP group (Control). In vivo experiments further disclosed that miR-203 greatly inhibited the growth of PCa tumors in nude mice. Markedly heightened expression of M1 macrophage markers such as IL-1β, IL-6, IL-12, CXCL9, and CXCL10 was observed within the tumor microenvironment following miR-203 intervention, as opposed to the model group. However, the introduction of miR-203 antagomir led to a reversal in tumor growth trends. This investigation indicates the presence of miR-203 within the urine of PCa patients and Exo originating from cells, and that miR-203 exerted antitumor effect by facilitating M1 macrophage polarization. Our study furnishes valuable insights into the potential applicability of miR-203 as a diagnostic biomarker and therapeutic target for PCa.

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All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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Acknowledgements

We are particularly grateful to all the people who have given us help on our article.

Funding

This research was supported by the General Project of Wuxi Municipal Health Commission (Project No. M202155).

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Author notes

  1. Lian-Sheng Zhang and Qi-Chao Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Soochow University Affiliated Wuxi Ninth Hospital, No. 999, Liangxi Road, Binhu District, Wuxi, 214000, Jiangsu Province, China

    Lian-Sheng Zhang, Hong-Tao Zong & Qiang Xia

  2. Department of Urology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu Province, China

    Qi-Chao Chen

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  1. Lian-Sheng Zhang
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Contributions

Conception and design of the research: Lian-Sheng Zhang, Qiang Xia Acquisition of data: Qi-Chao Chen Analysis and interpretation of the data: Hong-Tao Zong Statistical analysis: Qi-Chao Chen, Qiang Xia Obtaining financing: Lian-Sheng Zhang Writing of the manuscript: Lian-Sheng Zhang, Qiang Xia Critical revision of the manuscript for intellectual content: Lian-Sheng Zhang, Hong-Tao Zong, Qiang Xia All authors read and approved the final draft.

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Correspondence to Lian-Sheng Zhang or Qiang Xia.

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The authors declare that they have no competing interests.

Ethical approval

The study was reviewed and approved by the Medical Ethics Committee of Wuxi Ninth Hospital (No. KT2022013), and the animal experiments were followed strictly by the approved guidelines.

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Urine samples were obtained with the informed consent of the patients.

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Zhang, LS., Chen, QC., Zong, HT. et al. Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04854-5

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